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What We're Reading

Each issue of the Topics, Trends & Updates email includes a summary of a recently published journal article, written by Christopher Hoffmann, MD, MPH, Principal Investigator of the HIV Clinical Guidelines Program. Dr. Hoffmann is an assistant professor of medicine at the Johns Hopkins University School of Medicine, Division of Infectious Diseases. 

Articles are chosen to highlight topics that are directly relevant to clinical practice in the U.S. and that are not already widely summarized by other authors. 

All titles are listed below. If you would like to receive the Topics, Trends & Updates email, please subscribe

2017

2016

 

Vitamin D Deficiency Associated with Statin-Induced Muscle Toxicity in Patients Living with HIV (3/17)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine

A recently published study supports the association between statin-related myalgia and vitamin D deficiency among people treated with antiretroviral (ARV) agents, with an impressive effect size of 2.3 [Calza L, et al. AIDS 2017 Mar 13;31(5)].

Several antiretroviral (ARV) agents are associated with hypercholesterolemia. In addition, some ARVs, and a pro-inflammatory state caused by HIV itself, can increase the risk of cardiovascular disease (CVD). For these reasons, both hypercholesterolemia and CVD appear to be increased among people living with HIV. Statins play an important role in managing hypercholesterolemia and in reducing the risk of CVD, thereby reducing mortality, among patients living with HIV. The American College of Cardiology and the American Heart Association recommend statins for all individuals at high risk of cardiovascular disease [Stone NJ, et al. J Am Coll Cardiol. 2014 Jul 63(25 Pt B)]. Whether a role for statins exists among people living with HIV who are at low to moderate risk of cardiovascular disease is being evaluated in the REPRIEVE study.

Adherence to statin treatment can be compromised by muscle toxicity. In the general population, between 10% and 25% of individuals taking statins report having myalgia, and many discontinue the therapy as a result. Further, vitamin D deficiency has been associated with statin-induced myalgia in the general population. Given the frequency of vitamin D deficiency among people living with HIV (70%-84%), Calza and colleagues [AIDS 2017 Mar 13;31(5)] performed a retrospective analysis in Italy on a cohort of 545 patients taking ART and either atorvastatin or rosuvastatin. The primary study goal was to evaluate the association between vitamin D level and muscle toxicity using the following markers: myalgia, elevated creatinine kinase level in the absence of myalgia, or myalgia and elevated creatinine kinase level.

The majority of patients were male (80%) and white (91%); 95% had an undetectable viral load. Muscle toxicity was identified among 100 patients (18%), evidenced by myalgia in 42, elevated creatinine kinase without myalgia in 33, and elevated creatinine kinase with myalgia in 25. There was no statistically significant difference in muscle toxicity between patients taking atorvastatin or rosuvastatin. The median time to muscle toxicity was 412 days, with 10% of patients having toxicity within 34 days of starting a statin. Vitamin D deficiency was associated with muscle toxicity. Among patients with muscle toxicity, the vitamin D level was 19 to 22 ng/mL (depending on presence of myalgia or elevated creatinine kinase level), compared with a level of 32 ng/mL among patients without muscle toxicity. Among the 40 patients with a vitamin D level available at the time of myalgia or elevated creatinine kinase diagnosis, the level was similar to that at baseline. In an adjusted analysis, factors associated with muscle toxicity were age older than 60 years, history of myalgia, vitamin D levels lower than 30 ng/mL (odds ratio, 2.3), and longer duration on statin therapy. Notably, therapy with a boosted-protease inhibitor was not associated with an increased myalgia risk.

Two observational studies in the general population suggest that supplementing vitamin D when the level is low may reduce the occurrence of statin-related myalgia [Glueck CJ, et al. Curr Med Res Opin. 2011 Sep;27(9); Khayznikov M, et al. N Am J Med Sci. 2015 Mar;7(3)]. Randomized trials of vitamin D supplementation to reduce statin myalgia have not been completed in the general population or among people living with HIV. However, given the frequency of vitamin D deficiency in patients living with HIV and the potential benefits of a normal vitamin D level on bone health and immune activation [Overton ET, et al. Ann Intern Med. 2015 Jun16;162(12); Fabre-Mersseman V, et al. AIDS. 2014 Nov 28;28(18)], treating vitamin D deficiency with oral vitamin D3 supplementation is reasonable. Achieving a normal vitamin D level may also reduce statin-induced myalgia, increasing the chance of success with statin therapy and ultimately reducing cardiovascular disease.  

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Quality of Life Improvement with Early ART Initiation (2/17)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine 

Results of a just-published study suggest that, in addition to reducing all-cause mortality and improving health overall for patients with HIV infection, early initiation of ART also improves quality of life (QOL). Using data collected at baseline and during follow-up visits for the START trial, Lifson and colleagues assessed whether timing of ART initiation affected patients’ self-assessed QOL (Lifson, AR et al. AIDS. 2017 Apr 24;31(7)).

The START trial, which was conducted in 35 countries, randomized 4,685 participants with CD4 counts >500 cells/mm3 to one of 2 arms: immediate ART initiation or ART initiation at CD4 count <350 cells/mm3. Roughly 50% of participants lived in high-income countries and 50% in low- and middle-income countries. Approximately 75% received an initial ART regimen containing efavirenz, an agent well known to cause CNS and mood side effects.

At each study visit, patients were asked to assess their QOL using 2 methods–a visual analog scale to record their perceived current state of health (scored 0-100) and the SF-12, a widely used survey that includes physical and mental health components. 

QOL data were collected for 4,561 START trial participants, distributed evenly between the immediate and deferred ART study arms. At baseline, physical and mental health scores were similar between the two arms. By 4 months they diverged, with scores improving in the immediate ART arm and remaining relatively unchanged in the delayed ART arm. Scores of deferred ART patients were censored from analysis upon ART initiation.

The difference in QOL scores persisted: throughout 5 years of follow-up; when individuals with severe events were excluded; and through multiple subgroup analyses, including age, gender, race, geographic region, baseline CD4 count, efavirenz ART, and baseline visual analog scale.

This analysis provides further support for universal access to ART upon diagnosis of HIV infection: ART reduces severe health events, reduces HIV transmission, and improves quality of life for otherwise healthy people living with HIV.  

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A High Rate of Dolutegravir Side Effects in "Real-World" Settings (1/17)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine 

In my practice, 5% to 15% of the patients I start on dolutegravir (DTG) experience intolerable headaches or insomnia that necessitate a switch to another agent. This level of intolerance is higher than reported from clinical trials. I always wonder whether the patients of other clinicians have had the same “real-world” experience with DTG side effects and now several recent studies shed light on this issue. 

In one study, researchers from the Netherlands [de Boer MG, et al. AIDS. 2016 Nov 28;30(18)] reported on the tolerability of DTG among 556 patients initiated on DTG between August 2014 and March 2016. DTG was stopped in 76 patients (13.7%) due to adverse drug reactions after a median of 73 days (range 5-327). The combination of DTG with abacavir (ABC) led to a higher overall discontinuation rate (16.3%). The majority of side effects were neuropsychological or psychiatric (insomnia, headaches, mood alterations, and malaise) and gastrointestinal. Discontinuation for neuropsychiatric side effects was 2.3 times more likely among patients taking DTG plus ABC.

Other researchers have also reported neuropsychiatric side effects with DTG. Researchers in Germany [Hoffmann, C et al. HIV Med. 2017 Jan;18(1)] evaluated a cohort of 1,704 patients who initiated an ART regimen containing an integrase strand transfer inhibitor (ISTI) between January 2007 and April 2016. The rates of adverse events leading to discontinuation within 12 months were 7.6% for elvitegravir (EVG), 7.6% for DTG, and 3.3% for raltegravir (RAL). Renal side effects were the leading cause of EVG discontinuation (3.5%); neuropsychiatric side effects were most commonly reported with DTG (5.0%). The most common neuropsychiatric symptoms among the 49 patients who discontinued DTG were insomnia and other sleep disturbances, dizziness, headache, poor concentration or slowed thinking, depression, and painful paresthesia.

An older (2015) case series from France that includes four patients [Kheloufi, F et al. AIDS. 2015 Aug 24;29(13)] described the following symptoms post-DTG-initiation: fatigue and “drunk feeling” in patient 1, headaches and depression in patient 2, worsening psychiatric symptoms in patient 3, and intense headaches (which spontaneously resolved) followed by suicidal ideation in patient 4. 

DTG is a highly potent agent with a high barrier to resistance and unparalleled outcomes in randomized trials [Cahn, P et al. Lancet. 2013 Aug 24;382(9893); Clotet, B et al. Lancet. 2014 June 28;383(9936); Walmsley, SL et al. N Engl J Med. 2013 Nov 7;369(19)], and it appears to be very well tolerated in most patients who do not experience side effects. For these reasons, it has an important role in current antiretroviral therapy (ART). However, assessing for side effects and correctly identifying DTG as a potential cause of new and unexpected symptoms in the days to weeks after initiating this drug is essential to optimal care. My experience with the side effects with DTG has taken a little of the shine off this potent agent and has led me to consider the potential for DTG-associated side effects when selecting a regimen for an ART-naïve patient or planning a switch for failure or convenience.    

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Is Memory Really the Problem in ART Adherence? (10/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

An undetectable HIV viral load is the sine qua non of effective antiretroviral therapy (ART). Once the correct ART regimen is prescribed, achievement of an undetectable viral load then depends on sustained adherence. The authors of a recent study in AIDS Care (Kalichman SC, et al. AIDS Care. 2017 Apr;29(4).) sought to better understand and differentiate between factors associated with moderate and severe non-adherence. Moderate non-adherence was defined as 75% to 95% of medication doses taken as prescribed; severe non-adherence was defined as <75% of doses taken as prescribed.

The authors used computerized interviews to collect patient self-reported data on symptoms, side effects, use of common reminder strategies, depression, life stress, and alcohol consumption. The authors also used urine testing to assess for recent illicit drug use. Over a 1-month period, participants were contacted three times for telephone-based pill counts. Participants who had missed doses were then asked about cognitive, organizational, mental health, substance use, and structural barriers to adherence. 

The team followed 214 severely non-adherent and 342 moderately non-adherent participants for 1 month. A large and equal proportion of patients in each group used memory aids to support adherence, including pill boxes, alarms, routine timing of pills, journals, reminders from family members, or posted reminder signs. Although a larger proportion of the severely non-adherent participants reported having forgotten or having been too busy to take medications, the number was not statistically significant. Of the severely non-adherent, 54% reported forgetting compared with 41% of the moderately non-adherent. A larger and statistically significant difference in adherence was related to side effects, running out of pills, and consumption of alcohol (see table below). Depression and stress were also higher among severely non-adherent participants.

Factors Affecting ART Adherence Participants Reporting this Effect,          by Level of Non-Adherence
Severe Moderate
Medication side-effects 12% 4%
Running out of pills 21% 9%
Consumption of alcohol 21% 13%

The results of this study suggest that even when adherence reminder strategies are used, they are not effective in helping patients overcome factors related to both severe and moderate non-adherence, including, in this group, alcohol use, access to medications, and mental health challenges. 

This study did have some limitations. The researchers followed participants for just 1 month, and the results were not strong: 68% of the severely non-adherent had undetectable viral loads, and less than 50% of non-adherence among participants was associated with the factors named above.

Nonetheless, the results highlight the roles that mental health, substance use, and structural barriers may play in reducing adherence to ART. The findings also suggest that other, yet-to-be identified factors are at play as well. Perhaps most importantly, the standard focus on memory, reminders, and memory aids may not be helpful in significantly improving adherence among those with demonstrated non-adherence, and we need to dig deeper to help our patients take the medications that will suppress their viral loads.

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Successful Same-Day ART Initiation with a Complex Patient Population (8/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

A move to test and initiate treatment on the same day will require changes in traditional approaches to HIV management. Those changes may include restructuring clinic services and identifying individuals who are the best candidates for immediate antiretroviral therapy (ART) initiation. A recent article (Pilcher et al. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1)) describing immediate ART initiation by the San Francisco General Hospital outpatient HIV clinic provides insight into both issues.

Beginning in July 2013, the clinic began to offer same-day ART initiation with a protocol called RAPID. During the entire reported period (6/2013 to 12/2014), only patients lacking private insurance were eligible. In the first 6 months, eligibility for RAPID care was also limited to patients with acute or recent HIV infection, but criteria were liberalized after January 2014. Patients were referred from outpatient clinics and HIV testing centers in San Francisco, and taxi vouchers were available for patients to be transported from across the city. 

The RAPID protocol provided same day HIV education, blood draws for laboratory testing, accelerated insurance approval efforts, and a directly observed first ART dose. Patients for whom insurance approval was not obtained were given a 5-day starter-pack. This process took 3 to 4 hours. Within the 7 days after the initial visit, a nurse followed up by phone.

During the 18 month study period, 39 patients who would be considered “complicated” in most treatment settings were initiated on the RAPID protocol (2 patients per month). Patients’ CD4 counts ranged from 3 to 1391 cells/mm3, 27% were considered homeless, 42% had a “major” mental health disorder, and 42% reported use of any illicit substance. Despite these challenges, 37 patients (95%) initiated ART within 24 hours of their clinic visit. Approximately 90% had a viral load <200 copies/mL within 6 months after clinic referral. Only 4 (10%) were lost from care (no visit in a 6 month period); 8 (20%) transferred care to another clinic.

Although limited by its very small sample size and low volume of patients during the observation period (2 patients per month), this report is valuable for its description of a same-day ART initiation program that succeeded with complex patients. With the right clinical resources, these results suggest that most people living with HIV can initiate ART rapidly with success. This report also underscores that ART should not be delayed automatically because of mental illness, substance abuse, and/or unstable housing. 

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Blood Pressure Control and Medication Adherence among People Living with HIV (7/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

Hypertension is a common comorbidity among people living with HIV (PLH), affecting 20% to 43%. This proportion is likely to grow with the aging of the PLH population (see Okeke NL, et al. Clin Infect Dis 2016 Jul 15;63(2), for time trends in HTN diagnosis among PLH). Recent studies suggest the need to educate patients about the risks of uncontrolled hypertension (HTN).

The pivotal 2015 SPRINT study [SPRINT Research Group, et al. NEJM 2015 Nov 26;373(22)] quantified a reduction in mortality and cardiovascular outcomes with tight versus routine HTN control among individuals who were not HIV-infected. This large, randomized, controlled trial involved 9,361 individuals 50 years of age and older with a systolic blood pressure (SBP) between 130 and 180 mmHg (median 140 mmHg) and cardiovascular risk factors other than diabetes. Participants were randomized to one of two arms, with results reported after a median 3.3 years of follow-up. Results are summarized in the table below.

  Treatment Arm
Participants Standard Intensive
Number 4,683 4,678
Target SBP mmHg <140 <120
Median no. HTN meds 1.8 2.8
Serious adverse events 2.5% 4.7%
No. reaching primary clinical outcome
(hazard ratio = 0.75, p < 0.001)
319 243

The primary clinical outcome was defined as one of the following: myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death. All-cause mortality was also substantially lower (hazard ratio = 0.73, p = 0.003) in the intensive treatment arm. Approximately 38% of participants in each arm experienced side effects, although serious adverse events, such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury, were higher in the intensive treatment arm. In all, the SPRINT study demonstrated that a goal of SBP<120 mmHg reduced mortality and cardiovascular outcomes among individuals over the age of 50.

The PLH population already on antiretroviral therapy (ART) has experience with multiple medications and with regimens that require adherence as strict as those for HTN. 

Weiss and colleagues [J Acquir Immune Defic Syndr. 2016 Dec 1;73(4)] recently studied the effects of adding both medications and exhortations for strict adherence to the treatment regimens of HIV-infected participants. The researchers recruited 117 participants with HIV and HTN and 37 participants with HIV and chronic kidney disease (CKD) and followed them with health belief surveys and electronic monitoring of adherence to HIV, HTN, and CKD medications. At the 10 week follow-up, 88% of participants had virologic control and 60% had HTN control (SBP<140 mmHg). However, there was no difference in adherence to ART and HTN medications.

ART adherence was associated with participants’ reports of greater understanding of HIV, the perception of greater severity of HIV, and the view that ART medications are more necessary than medications for other conditions. This study suggests that HTN control is worse than virologic control among PLH, even though adherence to the two types of medication may be similar.

Taken together, the results of these two studies suggest that clinicians caring for PLH may need to intensify efforts to educate patients about HTN and its consequences and the potential benefit of a blood pressure even lower than the standard <140 mmHg. 

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Cardiovascular Risk Scores and CVD Risk Reduction among People Living with HIV (6/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

Primary methods of preventing cardiovascular disease (CVD) with smoking cessation, control of hypertension, and use of aspirin and HMG-CoA reductase inhibitors can substantially reduce the risk of myocardial infarction. Guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommend risk-based prescription of HMG-CoA reductase inhibitors. The ACC/AHA guidelines use a specific population-based risk calculator; however, other scores are also available, including the Framingham Risk Score and the D:A:D cardiac risk score for people living with HIV (PLH). Among PLH, it remains unclear how well these scores predict risk of myocardial infarction caused by plaque rupture.

Monroe and colleagues [Monroe AK, et al. AIDS. 2016 Aug 24;30(13)] used data from the Multicenter AIDS Cohort Study (MACS), a multisite longitudinal cohort of HIV-infected and -uninfected men who have sex with men, to assess the performance of risk calculators for predicting coronary atherosclerosis, coronary calcium, or coronary stenosis of greater than 50%, as measured using cardiac computed tomography (CT). The authors reported a poor association between cardiac risk score and the presence of any plaque (area under the curve is 0.65 for PLH; an area under the curve of 0.5 indicates no correlation). Among PLH who were at low risk according to the ACC/AHA formula, 36% had a coronary artery calcium score greater than 0, 63% had any plaque (calcified and non-calcified), and 11% had greater than 50% stenosis. Performance was marginally better for those without HIV infection; however, 53% with any plaque and 5.4% with greater than 50% stenosis were in the low-risk category.

There are several potential interpretations of these findings:

  • The MACS population is different from everyone else, and risk calculators do not apply.
  • Compared with the general population, PLH have different needs and risk profiles for some aspects of primary care, such as CVD risk management, and calculators may not be the best approach to CVD risk management in PLH.

Limitations of this study include its use of a cohort that is not representative of the general PLH population and its use of coronary calcium score and atherosclerosis on CT as opposed to hard endpoints, such as CVD events.

Studies such as this raise questions regarding use of HMG-CoA reductase inhibitors among PLH. In other words, are we treating the right people? The ongoing REPRIEVE clinical trial is aimed at helping to answer this question.

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Predicting Kidney Disease Risk to Guide ART Selection (4/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

Kidney disease is common among people living with HIV. Multiple factors, including HIV-associated nephropathy, antiretroviral therapy (ART), hepatitis B (HBV) or C (HCV) virus coinfection, diabetes, hypertension, and primary kidney disease can cause or contribute to kidney dysfunction. More common factors, though, are transient fluctuations in serum creatinine and estimated glomerular filtration rate (eGFR). Reducing the occurrence of comorbidities associated with kidney disease and limiting the diagnostic uncertainty of eGFR fluctuations may influence ART-prescribing decisions.

In a recently published article [AIDS 2016 Jun 1;30(9)], Flandre and colleagues report on the relationship between various initial ART regimens and the risk of chronic kidney disease (CKD). The researchers used a predictive score, developed and validated through the D:A:D cohort, that defined CKD as a persistent eGFR <60 mL per min per 1.73 m2.

The study cohort included 6,301 patients receiving care at 12 reference centers in France, all of whom initiated ART after January 1, 2004. All patients had at least one pre-ART and two on-ART creatinine measures, and eGFR was determined with the MDRD equation. Patients were stratified into low, medium, and high risk for CKD using the D:A:D score for CKD. This score accounts for a wide variety of factors, including type of HIV exposure (injection drug use [IDU] vs non-IDU), HCV coinfection, age, pre-ART eGFR, sex, nadir CD4 count, hypertension, cardiovascular disease, and diabetes. Incident CKD occurred in 211 (3.4%) of participants and was associated with older age, lower pre-ART eGFR, and lower nadir CD4 count. The probability of CKD by risk score was as follows: low risk, 0.65%; medium risk, 4.6%; and high risk, 15.9%.

CKD risk was highest for patients receiving a boosted protease inhibitor (PI) with tenofovir disoproxil fumarate (TDF). Risk was lower for patients receiving a non-nucleoside reverse transcriptase inhibitor (NNRTI) with or without TDF. Notably, among low-risk patients, the choice of an NNRTI vs a PI or TDF vs no TDF made no apparent difference in CKD risk.

This study is helpful in assessing the appropriateness of TDF or boosted-PI regimens for specific patients. For instance, avoidance of an initial ART regimen that includes TDF or a boosted-PI may be best for patients with a high D:A:D score for CKD. Patients with a low CKD risk score do not appear at increased risk for CKD from TDF or boosted PIs. These types of data may also be useful in securing insurer authorization to prescribe specific medications, such as tenofovir alafenamide (TAF)-containing combination tablets, and in discussing ART regimen side-effect profiles with patients.

Taking a risk-based approach when choosing an ART regimen does not require actual calculation, but taking into account a patient’s D:A:D score and risk factors for CKD is encouraged. Such an approach may reduce the number of patients requiring switches to less nephrotoxic regimens due to elevated eGFRs and may reduce the incidence of CKD among people living with HIV.

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Life Expectancy after an HIV Diagnosis (3/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

One of the first questions a patient newly diagnosed with HIV may ask is, “How long will I live?” A new study from CDC researchers, which reports data on life expectancy from the time of diagnosis and average years of life lost (AYLL)*, may help in answering that question [Siddiqi, et al. J Acquir Immune Defic Syndr 2016 Jun 1;72(2)].

Using CDC HIV Surveillance Report data from all 50 US states and the District of Columbia, the researchers estimated life expectancy by year of HIV diagnosis for individuals reported to have been diagnosed during the four years from 2008 to 2011.  Life expectancy was further stratified by HIV exposure category, sex, and race/ethnicity.  The authors did not consider post-diagnosis factors such as engagement in care or virologic suppression.

Overall, between 2008 and 2011, the average life expectancy at the time of HIV diagnosis increased by 3.5 years, from 25.4 to 28.9 years. By transmission category, life expectancy at the time of diagnosis in 2011 was highest (32.3 years) among men having sex with men (MSM); it was lowest (20.2 years) among men injecting drugs. Analysis by race indicated that life expectancy was highest among Hispanic/Latinos, followed by blacks, whites, and other races (range: 26.1 to 30.8 years). Average years of life lost were not similarly stratified. With regard to sex, for all men diagnosed at age 25, the AYLL was 16.8 years; for women diagnosed at age 25, AYLL was 23.2 years.

This analysis demonstrates continued overall improvement in HIV survival, which may reflect increasing efforts to engage people living with HIV in care and to initiate antiretroviral therapy (ART). However, the analysis also highlights discrepancies in survival by population group, which most likely reflects better engagement in care among MSM than among injection drug users. And while the study reinforces the value of ART for achieving longevity, its findings suggest that nearly normal life expectancy with HIV infection depends not only on access to ART for all patients but also on support to overcome systemic social, economic, and substance use challenges and maintain engagement in care and adherence to ART.

*AYLL is calculated by subtracting life expectancy with HIV from life expectancy for the general population. 

Detection of Invasive Anal Cancer in HIV-Infected Patients (1/16)

By Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine

Although invasive anal cancer is relatively rare, the disease can be devastating. The incidence of this cancer is increased among people living with HIV, especially among those who engage in receptive anal sex. For someone living with HIV in the United States or Canada, the cumulative incidence for anal cancer by the age of 65 has been estimated to be 1.3% compared with 0.03% for someone without HIV [Silverberg et al., Ann Int Med 2015 Oct 6;163(7)]. This cumulative incidence exceeds those for colorectal, liver, and pharyngeal cancer.

Clinical guidelines for prevention of anal cancer borrow heavily from the cervical cancer literature, with limited data to support specific screening and management practices. Routine screening generally includes anal cytology without HPV typing. A recent article by D’Souza and colleagues adds to the knowledge base of anal cancer. They studied the incidence and clearance of squamous intraepithelial lesions, as well as high-risk HPV infection, among HIV-infected and uninfected men who have sex with men (MSM) in the United States [J Acquir Immune Defic Syndr. 2016 Apr 15;71(5)]. The authors describe longitudinal follow-up for 1511 men with repeat anal cytology separated by 2 years; 723 were living with HIV; 788 did not have HIV. Most of those with HIV had undetectable viral loads (78%), and the median CD4 cell count was 583 cells/mm3. Abnormal cytology (of any kind) was identified among 40% of the men living with HIV and in 25% of those without HIV. Only 1.5% of men had high-grade squamous intraepithelial lesions. However, 2.4% had atypical squamous cells for which high-grade lesions could not be excluded. Among HIV-infected men who received repeat cytologic testing after initial ASCUS (atypical cells of undetermined significance) or low-grade squamous intraepithelial lesions, 56% regressed to normal cytology; 81% of those with high-grade cytologic findings regressed to a lower grade. High-risk HPV 16 was identified among 25% of men living with HIV and 16% of those without HIV. Among 220 men who received follow-up high-resolution anoscopy with biopsy after cytologic findings of high-grade lesions, 17% had histologically confirmed disease.

This study adds to the data on the high prevalence of anal HPV infection and cellular changes among MSM with HIV. It also highlights the limitation of cytology to identify individuals who should receive high-resolution anoscopy and biopsy, given the frequency of regression of lower-grade lesions to normal. Additional studies are underway that could shed more light on prevention of anal cancer and management of high- and low-grade lesions. Until results are available from those studies, the common practice of routine cytologic testing and referral for high-grade lesions, as well as for atypical squamous cells for which high-grade lesions cannot be excluded, remains a reasonable approach.

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ABOUT THE HIV CLINICAL GUIDELINES PROGRAM

Introduction: The HIV Clinical Guidelines Program is a collaborative effort of the New York State Department of Health (NYSDOH) AIDS Institute (AI), Office of the Medical Director (OMD), and the Johns Hopkins University (JHU) School of Medicine, Division of Infectious Diseases. 

History: When the HIV Clinical Guidelines Program was established in 1986, the complexity of HIV care and prevention and the need to integrate rapid changes into clinical practice necessitated a coordinated response to meet the practice and informational needs of clinicians, support service providers, and consumers. The HIV Clinical Guidelines Program met those needs by drawing on the experience of clinical experts familiar with providing medical care to New York State’s HIV-infected population. Since then, the program has successfully collaborated with a broad array of stakeholders and experts to develop HIV care and prevention guidelines that are current, clear, and accessible.

Over the course of its thirty-year history, the program has successfully addressed the broad spectrum of HIV care throughout the State, and with the expanded mission of the AI, now also addresses guidelines topics in HCV care, STI care, drug user health, and LGBT health.

Mission: The mission of the Clinical Guidelines program is to develop, disseminate, and guide the implementation of state-of the-art clinical practice guidelines to improve the quality of care provided to persons living with HIV, HCV, STIs, and related comorbidities in New York State.

Expert committees: Guideline committees are composed of clinical representatives from throughout NYS, who work in a variety of practice settings, to ensure that recommendations reflect broad experience and address the needs of patients in all areas of the state. 

The AIDS Institute Guidelines Model

The diagram below outlines the continuous process of the Clinical Guidelines Program. The process ensures the relevance, adaptability, and usefulness of the clinical guidelines to practitioners and contributes to the provision of clinically current, scientifically sound treatment for patients.

⇒ Development: Experts representing multiple specialties collaborate to draft scientifically sound, clinically current guidelines for the care of adults and adolescents living with HIV infection.

⇒ Dissemination: Guidelines are disseminated through multiple channels to key target audiences using the resources of numerous AIDS Institute programs.

⇒ Implementation: Comprehensive implementation strategies promote broad adoption and integration of guideline recommendations into the daily practice of HIV care providers throughout New York State.

⇒ Evaluation: Evaluation activities increase understanding of guideline adoption and identify areas for improvement to ensure delivery of high-quality HIV care.

After clinical practice guidelines are developed, the HIV Clinical Guidelines Program actively disseminates those guidelines through a coordinated plan to reach all key audiences through email, website dissemination, the Clinical Education Initiative, social media, and other AIDS Institute resources. Expanded dissemination also involves production and distribution of clinical aids and point-of-care materials, as well as consumer material.

The Clinical Guidelines Program and the AIDS Institute Quality of Care Program work together to promote implementation of guidelines in New York State. The AIDS Institute routinely communicates information regarding best practices and practical solutions so that this information can be widely adopted by service providers. Program standards that govern service delivery in specific types of healthcare facilities encourage adoption of guideline recommendations. To enhance consumer understanding of the guidelines, the AIDS Institute develops and provides materials in multiple formats, sponsors consumer educational programs, and invites consumers who serve on the Consumer Advisory Committee to review all guidelines.

Johns Hopkins Clinical Guidelines Program: The Johns Hopkins University (JHU) School of Medicine, Division of Infectious Diseases, has collaborated with the New York State Department of Health AIDS Institute since 1999 to develop and disseminate the AIDS Institute’s HIV clinical guidelines and related quality-of-care information. This website is managed by the JHU program.

Funding: The Clinical Guidelines Program is supported by New York State funds allocated through a grant to the JHU School of Medicine to support all activities of the program.

 

 

Program Leadership and Staff

New York State Department of Health AIDS Institute

The Office of the Medical Director directs the program.

  • Bruce D. Agins, MD, MPH, Medical Director
  • Lyn Stevens, MS, NP, ACRN, Deputy Director
  • Charles J. Gonzalez, MD, Associate Medical Director for Science and Policy
  • Laura Duggan Russell, MPH, Program Coordinator

The AIDS Institute OMD consists of public health professionals dedicated to enhancing the quality of life for persons with HIV by improving prevention and health care services through performance measurement and science-based initiatives. The Office of the Medical Director oversees numerous programs and initiatives including:

Johns Hopkins University School of Medicine Clinical Guidelines Program

The Johns Hopkins University School of Medicine, Division of Infectious Diseases, has collaborated with the NYSDOH AIDS Institute since 1999 to develop and disseminate HIV clinical guidelines and related quality-of-care information.

Principal Investigator Christopher J. Hoffmann, MD, MPH provides leadership and strategic to the program and lends extensive experience in both HIV clinical care and guidelines development, as well as a resolute commitment to training for HIV care providers.

The JHU team manages all aspects of guidelines development and dissemination and program administration through the efforts of the following program staff:

  • Mary Beth Hansen, MA, Project Director
  • Christina Norwood, MS, ELS, Senior Editor
  • Jennifer R Ham, MPH, Medical Editor
  • Johanna L Gribble, MA, Medical Editor
  • Jesse M Ciekot, Program Coordinator

Contact Information

JHU: This website is managed and maintained by the staff of the JHU HIV Clinical Guidelines Program. If you have questions about the website or about the JHU HIV Clinical Guidelines program, please send an email to: webmaster@hivguidelines.org.

Mailing address: JHU HIV Clinical Guidelines Program, 2700 Lighthouse Point East, Suite 260, Baltimore, MD, 21224

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Mailing address: New York State Department of Health AIDS Institute, Office of the Medical Director, 90 Church Street, 13th Floor, New York, New York 10007-2919

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Guideline Development and Committees

Expert Committees

Composition: The Clinical Guidelines Program works directly with committees composed of experts in the field who represent multiple disciplines (medicine, nursing, psychology, pharmacy, public health, social work, mental health), clinical specialties (infectious diseases, family medicine, obstetrics and gynecology, hepatology, pediatrics, psychiatry, dentistry, prevention, etc.), and various geographic regions of New York State.

A Clinical Guidelines Program Steering Committee provides oversight and strategy to the following Clinical Guidelines Program committees, each of which is responsible for developing and updating clinical practice guidelines that fall under its area of expertise. Current committees (November 2016) include the following:

Financial disclosure and confidentiality agreement: All potential and active committee members are required to sign a confidentiality agreement and to disclose annually all financial relationships with commercial entities or gifts that may be actual, potential, or perceived as conflicts of interest. Committee members must report financial relationships with commercial entities that have existed in the 12 months prior to or are expected to exist in the 12 months after the date on which they sign their disclosure form.

Guideline development process: When the Clinical Guidelines Program identifies the need to develop or update a guideline, the committee under whose purview the guideline falls convenes to determine the goals of the guideline and its content, review the published literature, and weigh new evidence for recommendations. Text is then drafted by an author who has experience with the topic of the guideline.  The guideline draft is edited by the team at JHU, and then reviewed and modified by the committee. This rigorous development process may entail multiple rounds of review, revision, rating and editing. Decision making occurs by consensus, and all guideline recommendations are reviewed by and receive the consensus approval of the full guideline committee. 

Evidence-based Recommendations: All recommendations are rated to reflect the strength of each recommendation and the quality of the supporting evidence. Ratings are reached through review of the evidence and consensus decision. If the published evidence in support of a particular recommendation is not sufficient, the group relies on collective best practices experience to develop a final statement. The rating scheme for recommendations appears below.

Recommendation Rating Scheme: 

  • Strength of recommendation: A (Strong), B (Moderate), C (Optional)
  • Quality of evidence: I (One or more randomized trials with clinical outcomes and/or validated laboratory endpoints), II (One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes), III (Expert opinion)

External review: All guidelines are reviewed by external experts in the field and by the AIDS Institute’s Consumer Advisory Committee. 

Final approval: The guideline is submitted to the AIDS Institute for review and final approval prior to publication. The AI may request additional review by other agencies and organizations when applicable.

Guideline Updates: Members of guideline committees monitor developments ongoing to maintain guideline currency, at regular intervals. Newly published data that provides support for existing recommendations will be cited in the text and the studies will be added to the reference list. If newly published data prompts a revision to recommendations or rationale, a planning committee proposes appropriate edits and determines whether any changes warrant full committee review and approval. 

About this Website

Purpose

The HIV Clinical Resource website publishes the clinical practice guidelines and related materials produced by the Clinical Guidelines Program. The program is a collaborative effort of the New York State Department of Health AIDS Institute’s Office of the Medical Director (OMD) and the Johns Hopkins University School of Medicine, Division of Infectious Diseases. This website is maintained and managed by the JHU Clinical Guidelines program, within the Johns Hopkins University School of Medicine, Division of Infectious Diseases. 

Production and Development 

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This website is produced and maintained by the JHU Clinical Guidelines Program in the Johns Hopkins University (JHU) School of Medicine, Division of Infectious Diseases. The site does not does not purport to advance any official positions of JHU, the JHU School of Medicine, or the Division of Infectious Diseases. The JHU Clinical Guidelines Program, in collaboration with the New York State Department of Health (NYSDOH) AIDS Institute (AI) maintains editorial control of all materials published on this site, and unless noted otherwise, all materials posted on this site have been produced under the auspices NYSDOH AIDS Institute Clinical Guidelines Program.

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The JHU Clinical Guidelines Program does not provide clinical care and does not provide clinical or medical advice. 

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The JHU Clinical Guidelines Program recognizes the importance of protecting the privacy of visitors to the HIV Clinical resource website and of subscribers to the site mailing list and to the monthly Topic, Trends, and Updates e-mail update.

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While every possible effort if made to post accurate and reliable information on this website, neither the JHU HIV Clinical Guidelines Program, neither the JHU HIV Clinical Guidelines Program, nor The Johns Hopkins University nor The Johns Hopkins School of Medicine, nor the NYSDOH AIDS Institute HIV Clinical Guidelines Program assumes responsibility for the use or application of information posted on any page of this website or guarantees or warrants that the information posted on any page of this site is complete and without any error or inaccuracy. The website, its editors, advisors, staff, authors, and sponsoring institutions assume no responsibility for any error, omissions, or other discrepancies between the electronic documents published on this site and source materials.

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This website links to websites maintained by other entities. Reasonable precautions are taken to link only to websites that publish appropriate and accurate material and are maintained by reputable organizations. However, those web pages are not under the direction or control of this website, and this website can therefore not be held responsible for the information or opinions expressed in those linked sites.

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The use, reproduction, and distribution of original documents and related graphics from this web site is encouraged provided that full credit of source accompanies all uses, in all forms. Please note that if we have adapted or reproduced copyrighted material from another source, with permission, we cannot extend permission to reproduce. Links to pages on this site are also encouraged and may be created without seeking permission.

Any use of materials from this site should be accompanied by the following citation of source: 

This material was accessed on [dd/mo/year] on the HIV Clinical Resource website (www.hivguidelines.org). The HIV Clinical Guidelines Program is a collaborative effort of the New York State Department of Health AIDS Institute and the Johns Hopkins University Division of Infectious Diseases. Copyright © Johns Hopkins University HIV Clinical Guidelines Program 2000-2016. 

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Contact Us

Mailing address:

JHU HIV Clinical Guidelines Program
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E-mail addresses:

We will make every effort to answer e-mail submitted to any of the above addresses within 48 hours.

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ADULT HIV CARE

The Medical Care Criteria Committee (MCCC) and its invited affiliates produce the adult HIV guidelines

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Testing and Diagnosis Guidelines

HIV Testing Guideline

Diagnosis and Management of Acute HIV Infection Guideline

HIV Testing in the Oral Health Care Setting Guideline

Dental Standards of Care Committee, October 2015

Rationale and Recommendations

Purpose of this guideline: This document provides key recommendations for implementing an HIV testing program in the oral health care setting. A more detailed guide to implementing HIV testing programs in oral health care settings has been developed by the New York State Department of Health AIDS Institute in collaboration with the New York/New Jersey AIDS Education and Training Center (AETC) Oral Health Regional Resource Center and includes an algorithm that can be used as a planning tool. For more information, see HIV Testing in the Dental Chair: Technical Assistance Manual and HIV Testing in the Dental Chair Algorithm. Additional resources are listed below.

Increasing HIV testing in New York State: In April 2014, sections of the New York State Public Health Law relating to HIV testing and confidentiality of HIV reports were amended to increase HIV testing in New York and promote linkage and retention in care for HIV-infected persons [1]. In 2010, the Amended HIV Testing Law [2] required healthcare providers to offer HIV testing as a routine part of healthcare to all persons aged 13-64 years (and others depending on risk). The 2014 Amended HIV Testing Law streamlines the testing process by no longer requiring written patient consent under most circumstances.

An estimated 12.8% of HIV-infected individuals in the United States were living with undiagnosed HIV infection in 2012 [3]. Routine HIV testing at the point of care is intended to identify more undiagnosed HIV-infected people, provide the benefit of earlier access to treatment, and reduce the risk of HIV transmission. In 2013, 61.7% of adults 18 to 64 years of age visited a dentist [4], highlighting the dental setting as a key opportunity for routine HIV testing.

RECOMMENDATIONS
  • Oral health care settings that can support an HIV testing program should offer testing to all dental patients. Diagnostic HIV tests must be performed in full compliance with the New York State Public Health Law; written consent is no longer required for HIV testing under most circumstances.
  • When oral health care settings provide testing, providers must:
  • Whenever there is a reactive result on an HIV screening test, the oral health care provider or a representative must:
    • Explain the result to the patient, including the requirements for follow-up diagnostic testing and consultation with an HIV provider
    • Immediately collect a blood specimen (i.e., finger stick or venipuncture) for follow-up diagnostic testing
    • Schedule an appointment for follow-up HIV medical care for the patient (see the NYSDOH HIV Patient Resources Directory for an interactive map of HIV care providers in New York State)
    • Ensure that the diagnostic test results are forwarded to the medical facility where the appointment has been made
  • Oral health care providers should develop referral agreements for timely appointments with medical providers who have experience with HIV treatment, management, and counseling.

Screening patients for HIV infection can be performed in oral health care settings. Factors to consider for implementing an HIV testing program include physical space that affords patient confidentiality, laboratory quality assurance, and staff training.

HIV testing is voluntary. Like all healthcare settings that offer HIV testing, oral health care settings must notify patients prior to testing that an HIV test will be conducted and must document every HIV test in the patient’s dental record. Written consent is no longer required for HIV testing under most circumstances; written informed consent is still required when HIV testing is performed in state and local prisons or jails. The oral health care team can easily perform HIV tests as part of routine care. For more information about implementing routine HIV testing in the oral health setting, see HIV Testing in the Dental Chair: Technical Assistance Manual.

If an HIV screening test indicates a reactive result, the test is considered a preliminary positive result. Whenever there is a reactive result on an HIV screening test, regardless of whether it is an oral fluid test or blood test, the oral health care provider, or a representative of the provider, who performed the HIV screening must collect a blood specimen for diagnostic testing and submit the specimen to a certified laboratory for analysis. Finger stick blood specimens should be sent to the Wadsworth Center, NYS Public Health Laboratory, for analysis. For information about the Wadsworth Center, call (518) 474-4177.

Oral health care providers must make an appointment for patients with a preliminary positive result to be seen, preferably within 48 hours, by a medical provider who has experience with HIV treatment [5]. Oral health care providers must ensure that the diagnostic test results are forwarded to the medical facility where the patient has been referred. Patients who express concern about their ability to afford HIV care may obtain information about financial assistance by visiting NYSDOH HIV Uninsured Care Programs Summary.

The New York State Department of Health provides resources to promote HIV testing as part of routine healthcare. One such resource, Testing Toolkit: Resources to Support Routine HIV Testing for Adults and Teens, presents information about the healthcare settings and healthcare professionals who are affected by the law. A broad range of topics is covered, including confidentiality, informed consent, communicating in a language that the patient can understand, key points that patients must be provided before HIV testing is performed, and follow-up for patients with confirmed positive test results. Additional online HIV testing resources are provided below.

Confidentiality laws regarding testing extend to physicians, physician assistants, oral health care providers, nurses, and other healthcare professionals. Oral health care clinics that provide HIV testing are subject to the same requirements as all healthcare settings and personnel who perform HIV testing. HIV testing must be conducted in accordance with applicable New York State public health laws and regulations.

Information about the HIV testing Public Health Law, consent forms, and counseling can be found at NYSDOH HIV Testing.

Resources

HIV Testing

Provider Directories

HIV Education and Training

Patient Materials for Providers

Online Resources for Patients

  • Information for Patients Who Test Negative for HIV
  • AIDS Institute HIV Patient Resources Directory: Provides a list of organizations funded by the New York State Department of Health AIDS Institute to provide HIV/AIDS services. This directory is arranged by region, with each organization listed under the region it serves and then by the type of service it provides.
  • HIV Uninsured Care Programs: These four programs, established by the New York State Department of Health’s AIDS Institute, provide access to free health care (HIV Drugs, Primary Care, Home Care, and APIC) for New York State residents with HIV infection who are uninsured or underinsured.
References:
  1. New York State Department of Health. HIV Testing: Public Health Law 2014 Amendments. Available at: www.health.ny.gov/diseases/aids/providers/testing
  2. New York State Department of Health. HIV Testing: Public Health Law: Chapter 308 of the Laws of 2010, HIV Testing Law, Mandated Report, August 2012. Available at: www.health.ny.gov/diseases/aids/regulations
  3. Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 dependent areas—2013. HIV Surveillance Supplemental Report 2015;20(No. 2). Published July 2015. Available at: www.cdc.gov/hiv/library/reports/surveillance
  4. Strauss SM, Alfano MC, Shelley D, et al. Identifying unaddressed systemic health conditions at dental visits: Patients who visited dental practices but not general health care providers in 2008. Am J Public Health 2012;102:253-255. [PubMed]
  5. New York State Department of Health AIDS Institute’s Oral Health Regional Resource Center (NY/NJ AETC). HIV testing in the dental chair: Technical assistance manual. Available at: www.nynjaetc.org/Testing.html

 

 

HIV Testing in Labor and Delivery Guideline

Provider Guide to HIV Testing (Quick Reference Guide)

Management of IRIS Guideline

Introduction: Immune Reconstitution Inflammatory Syndrome (IRIS)

Medical Care Criteria Committee, August 2009

The goal of ARV therapy in immunocompromised HIV-infected individuals is immune reconstitution. However, an aberrant manifestation of this effect sometimes occurs. Immune reconstitution inflammatory syndrome (IRIS), also known as immune restoration disease, refers to a disease- or pathogen-specific inflammatory response in HIV-infected patients that may be triggered after:

  • Initiation or re-initiation of ARV therapy
  • Change to more active ARV therapy

IRIS is usually accompanied by an increase in CD4 cell count and/or a rapid decrease in viral load. Although most cases of IRIS occur in patients who have low CD4 counts and high viral load levels at the time ARV therapy is initiated, IRIS can occur at any CD4 count. The time of presentation is usually within the first 4 to 8 weeks after initiation of ARV therapy; however, IRIS has occurred many weeks after initiation and in sequestered sites, such as bone [1].

After immune reconstitution, inflammatory reactions to many pathogens have been described, including mycobacterium, fungi, virus, and bacteria (see Presentation and Diagnosis). IRIS that involves worsening of some malignancies, including Kaposi’s sarcoma [2], and autoimmune phenomena have also been documented.

Epidemiologic data regarding IRIS are variable and depend largely on the incidence and types of infections that patients have at the time of initiation of ARV therapy. In the United States, retrospective studies have reported IRIS in 63% of HIV-infected patients who had inactive CMV retinitis at the time of initiation of ARV therapy [3] and 30% to 34% of those with inactive cryptococcus [4,5]. Similar rates have been found retrospectively in 30% and 31% of HIV-infected patients with Mycobacterium tuberculosis and M. avium complex (MAC), respectively [5]. However, retrospective studies may overestimate the incidence of IRIS. A prospective ACTG study, ACTG A5164, reported a rate of 7.6% [6]; however, this rate may have been low because most of the reported opportunistic infections (OIs) were PCP. Steroid treatment for PCP may have mitigated IRIS-related symptoms and reduced the number of IRIS diagnoses in the study.

KEY POINT
  • Caution and clinical judgment are required when implementing these guidelines because no prospective or randomized trials of treatments for IRIS exist; therefore, the recommendations here are based on small case series and expert opinion.

For further OI-specific guidance on management of IRIS, see Guidelines for Prevention and Treatment of Opportunistic Infections Guidelines issued by the NIH, CDC, and HIVMA/IDSA [1].

References:
  1. Adult Prevention and Treatment of Opportunistic Infections Guidelines Working Group. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents [DRAFT]. June 18, 2008; pp 1-289. Available at: http://aidsinfo.nih.gov/contentfiles/Adult_OI.pdf
  2. Feller L, Anagnostopoulos C, Wood NH, et al. Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: A literature review and case report. J Periodontal 2008;79:362-368. [PubMed]
  3. Karavellas MP, Plummer DJ, Macdonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infect Dis 1999;179:697-700. [PubMed]
  4. Shelburne SA 3rd, Darcourt J, White AC Jr, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 2005;40:1049-1052. [PubMed]
  5. Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-406. [PubMed]
  6. Grant P, Komarow L, Sereti I, et al. Risk factor analyses for immune reconstitution inflammatory syndrome and mortality during a randomized trial of early versus deferred ART in the setting of acute opportunistic infections: ACTG A5164. Sixteenth Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009, Montreal Canada.

Pathogenesis

August 2009

The pathogenesis of IRIS is largely speculative. Although one common aspect of IRIS cases is a significant increase in CD4 cells after initiation of ARV therapy in patients who had low CD4 cells prior to treatment [1-4], the pathogenesis of the inflammatory response may not be the CD4 cell increase. Instead, patients who develop IRIS may have preexisting perturbations in their T-regulatory cell profile and proinflammatory and regulatory responses, such as cytokine imbalances, that may significantly contribute to onset of the syndrome after initiation of an ARV regimen that is highly active against HIV in a given patient [5,6]. IRIS may also be more severe in patients with a higher burden of organism, which also suggests that antigen load may play a role [1].

References:
  1. Shelburne SA 3rd, Darcourt J, White AC Jr, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 2005;40:1049-1052. [PubMed]
  2. Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-406. [PubMed]
  3. Breton G, Duval X, Estellat C, et al. Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Clin Infect Dis 2004;39:1709-1712. [PubMed]
  4. Battegay M, Nüesch R, Hirschel B, et al. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis 2006;6:280-287. [PubMed]
  5. Shankar EM, Vignesh R, Velu V, et al. Does CD4+CD25+foxp3+ cell (Treg) and IL-10 profile determine susceptibility to immune reconstitution inflammatory syndrome (IRIS) in HIV disease? J Inflamm (Lond) 2008;5:2. [PubMed]
  6. Boulware D, Meya D, Bergemann T, et al. Inflammatory biomarkers in serum predict HIV immune reconstitution inflammatory syndrome and death after cryptococcal meningitis. Sixteenth Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009, Montreal Canada.

When to Initiate ART in Patients with Recent OIs

August 2009

RECOMMENDATION
  • Clinicians should strongly recommend that patients recovering from acute OIs initiate ARV therapy as soon as tolerability has been established and the potential for drug-drug interactions has been minimized (see Antiretroviral Therapy).

No consensus has been reached concerning the optimal time to initiate ARV therapy in patients with a recently diagnosed OI. In some cases, determination of the optimal timing for initiating therapy in these patients is complex and may require consultation with an experienced HIV provider.

The ACTG A5164 study suggests that benefits from immediate initiation of ARV therapy, particularly in the setting of PCP, outweigh the risks for IRIS [1]. Accordingly, clinicians should strongly recommend that patients recovering from acute OIs, such as those resulting from cryptosporidiosis, microsporidiosis, progressive multifocal leukoencephalopathy (PML), Kaposi’s sarcoma, PCP, and serious bacterial infections, initiate ARV therapy as soon as tolerability has been established and the potential for drug-drug interactions has been minimized.

Increasing the length of time between treatment of known TB and MAC and initiation of ARV therapy by 60 days has been shown to decrease the incidence of IRIS in those diseases [2,3]. However, the benefits of early initiation of ARV therapy in patients with active TB and very low CD4 counts (<50 cells/mm3) likely outweigh the risks for morbidity associated with TB-IRIS [4,5]. Careful monitoring for IRIS, and timely treatment if it occurs (see Preventing Complications and Management and Treatment), may significantly reduce morbidity associated with mycobacterium-related IRIS while also ensuring that other risks associated with severe immunosuppression are managed effectively with ARV therapy.

KEY POINT
  • Although the risk for TB-IRIS may be as high as 32% in severely immunocompromised patients [4], the overall mortality associated with delayed initiation of ARV therapy in these patients is greater than any potential risk of death resulting from IRIS [5].
References:
  1. Grant P, Komarow L, Sereti I, et al. Risk factor analyses for immune reconstitution inflammatory syndrome and mortality during a randomized trial of early versus deferred ART in the setting of acute opportunistic infections: ACTG A5164. Sixteenth Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009, Montreal Canada.
  2. Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-406. [PubMed]
  3. Schiffer JT, Sterling TR. Timing of antiretroviral therapy initiation in tuberculosis patients with AIDS: A decision analysis. J Acquir Immune Defic Syndr 2007;44:229-234. [PubMed]
  4. Lawn SD, Myer L, Bekker LG, et al. Tuberculosis-associated immune reconstitution disease: Incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 2007;21:335-341. [PubMed]
  5. Battegay M, Fehr J, Flückiger U, et al. Antiretroviral therapy of late presenters with advanced HIV disease. J Antimicrob Chemother2008;62:41-44. [PubMed]

Presentation and Diagnosis

August 2009

RECOMMENDATION
  • Clinicians should consider IRIS when inflammatory signs or symptoms occur after recent initiation, re-initiation, or change to a more effective combination ARV therapy with associated increase in CD4 cell count and/or decrease in viral load and the following have been excluded:
    • Worsening of known infections due to inadequate or inappropriate therapy (AIII)
    • New infections not known to be associated with IRIS (e.g., bacterial sepsis) (AIII)
    • Medication reaction (AIII)

Proposed case definitions do not provide clear consensus on the many manifestations of IRIS [1-4]. However, some well-established clinical syndromes exist, including fever and/or unmasking or worsening of previously quiescent or mild underlying disease symptoms. If the pathogen or condition provoking the inflammatory response was previously undiagnosed, the IRIS response is termed unmasking. Exacerbation or recurrence of symptoms from a previously known or treated disease is termed paradoxical worsening.

IRIS symptoms range from mild to severe but do not appear to have favorable or unfavorable implications for patient survival, with the exception of IRIS associated with cryptococcal meningitis [5,6]. The majority of IRIS cases occur within 4 to 8 weeks after initiation of or change in ARV therapy. However, the time until presentation can vary, with cases reported as few as 3 days and as many as several years after ARV therapy initiation. Late manifestations of IRIS (>7 months) may demonstrate atypical manifestations, such as osteomyelitis resulting from MAC [7]. The presentation of IRIS will vary depending on the underlying OI or illness.

The spectrum of signs and symptoms of IRIS often poses a challenge to diagnosis. The diagnosis of IRIS is based on clinical judgment, and multiple diagnoses can be present. The somewhat characteristic presentations of many OIs may aid in the diagnosis of IRIS.

Major Presentations of IRIS

Tuberculosis: Patients responding to TB treatment may have worsening of pulmonary symptoms or X-ray findings that indicate worsening of TB disease, enlarging lymph nodes, or meningeal symptoms [8].

  • TB-IRIS can also result in hepatotoxicity, which may be difficult to distinguish from medication-induced toxicity [9].
  • Multidrug-resistant TB may increase the risk for IRIS [10].

Mycobacterium avium complex: May present as localized lymphadenitis, pulmonary disease, or systemic inflammation that are indistinguishable from active MAC. Patients with MAC-IRIS are not bacteremic [11].

Cryptococcus: Usually presents as worsening of meningitis symptoms [6,8,12-14].

Cytomegalovirus: Presents as retinitis, vitritis, or uveitis:

  • Retinitis is inflammation that is usually at the site of previous CMV retinitis lesions
  • Uveitis and vitritis are the presence of inflammatory cells in the eye as a result of IRIS and may help to distinguish IRIS from active CMV retinitis [15]
  • IRIS due to CMV in the eye can cause rapid and permanent vision loss
  • The time to IRIS is variable; in one study, the median time to immune reconstitution vitritis was 20 weeks after initiation of ARV therapy [15]

Hepatitis B or C: Transient elevations in transaminases may occur after initiation of ARV therapy with immune reconstitution and can be difficult to distinguish from drug-induced hepatitis. Hepatic flares are usually mild and self-limited but can result in decompensation in someone with preexisting cirrhosis

Progressive multifocal leukoencephalopathy: PML lesions may be unmasked or worsen and could appear as new or worsening focal neurologic deficits or lesions on MRI scans [14,16,17].

Kaposi’s sarcoma: Presents as worsening of Kaposi’s sarcoma [18]. Fatal IRIS has occurred in patients with preexisting Kaposi’s sarcoma and multicentric Castleman disease after initiating ARV therapy [5]. The frequency of human herpesvirus-8-associated IRIS is not known [5].

Autoimmune diseases: Preexisting autoimmune disorders such as sarcoidosis or Grave’s disease may be exacerbated.

Minor Presentations of IRIS

Herpes simplex virus and varicella zoster virus: HSV and VZV can reactivate after initiation of ARV therapy. Presentations are usually similar to non-IRIS disease; however, IRIS may worsen a patient’s symptoms. Some patients become aware of their HSV infection only after the presentation of IRIS.

Nonspecific dermatologic complications: A number of dermatologic manifestations, such as folliculitis and oral and genital warts, may appear or worsen during immune reconstitution.

References:
  1. Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-406. [PubMed]
  2. French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 2004; 18:1615-1627. [PubMed]
  3. Robertson J, Meier M, Wall J, et al. Immune reconstitution syndrome in HIV: Validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy. Clin Infect Dis 2006;42:1639-1646. [PubMed]
  4. Shelburne SA, Montes M, Hamill RJ. Immune reconstitution inflammatory syndrome: More answers, more questions. J Antimicrob Chemother 2006;57:167-170. [PubMed]
  5. Adult Prevention and Treatment of Opportunistic Infections Guidelines Working Group. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents [DRAFT]. June 18, 2008; pp 1-289. Available at:http://aidsinfo.nih.gov/contentfiles/Adult_OI.pdf
  6. Kambugu A, Meya DB, Rhein J, et al. Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy. Clin Infect Dis 2008;46:1694-1701. [PubMed]
  7. Aberg JA, Chin-Hong PV, McCutchan A. Localized osteomyelitis due to Mycobacterium avium complex in patients with human immunodeficiency virus receiving highly active antiretroviral therapy. Clin Infect Dis 2002;35:E8-E13. [PubMed]
  8. Shelburne SA 3rd, Darcourt J, White AC Jr, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 2005;40:1049-1052. [PubMed]
  9. Lawn SD, Wood R. Hepatic involvement with tuberculosis-associated immune reconstitution disease. AIDS 2007;21:2362-2363. [PubMed]
  10. Meintjes G, Rangaka MX, Maartens G, et al. Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance. Clin Infect Dis 2009;48:667-676. [PubMed]
  11. Lawn SD, Bekker LG, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis 2005;5:361-373. [PubMed]
  12. Lortholary O, Fontanet A, Mémain N, et al. for the French Cryptococcosis Study Group. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS 2005;19:1043-1049. [PubMed]
  13. Lawn SD, Bekker LG, Myer L, et al. Cryptococcocal immune reconstitution disease: A major cause of early mortality in a South African antiretroviral programme. AIDS 2005;19:2050-2052. [PubMed]
  14. Gray F, Bazille C, Adle-Biassette H, et al. Central nervous system immune reconstitution disease in acquired immunodeficiency syndrome patients receiving highly active antiretroviral treatment. J Neurovirol 2005;11(Suppl 3):16-22. [PubMed]
  15. Karavellas MP, Plummer DJ, Macdonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infect Dis 1999;179:697-700. [PubMed]
  16. Safdar A, Rubocki RJ, Horvath JA, et al. Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: Impact of antiretroviral therapy-associated immune reconstitution. Clin Infect Dis 2002;35:1250-1257. [PubMed]
  17. Tan K, Roda R, Ostrow L, et al. PML-IRIS in patients with HIV infection: Clinical manifestations and treatment with steroids. Neurology 2009. In press. [PubMed]
  18. Feller L, Anagnostopoulos C, Wood NH, et al. Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: A literature review and case report. J Periodontal 2008;79:362-368. [PubMed]

Preventing Complications

August 2009

RECOMMENDATIONS
  • Clinicians should be alert to the possibility of IRIS as CD4 cell counts are restored after initiation of ARV therapy. (AIII)
  • After initiation of ARV therapy, HIV-infected patients with a history of CMV retinitis should be monitored for possible IRIS by dilated ophthalmologic examination:
    • Every 3 months for the first year after initiation of ARV therapy (AIII)
    • Immediately if there is a change in visual acuity or development of floaters (AIII)
  • For HIV-infected patients who are co-infected with hepatitis B or C, clinicians should measure transaminase levels:
    • Before initiation of ARV therapy (AI)
    • Monthly for the first 3 months after initiation of ARV therapy to monitor for possible immune reconstitution inflammatory syndrome (AIII)

Prevention of complications associated with IRIS involves careful monitoring, particularly in patients with low CD4 counts and a past or current history of co-infections. After initiating ARV therapy, clinicians should be alert to the possibility of IRIS as CD4 cell counts are restored.

A high index of suspicion for ophthalmologic manifestations of IRIS after initiation of ARV therapy, particularly among patients with low CD4 counts at the start of therapy, is warranted to avoid complications resulting from CMV. Patients with a history of CMV retinitis, even if receiving treatment, should receive a dilated ophthalmologic examination every 3 months for the first year after initiation of ARV therapy and immediately if there is a change in visual acuity or development of floaters. Cases of CMV-IRIS myelopathy that respond to steroids have been reported, as have cases of CMV-IRIS colitis [1,2]. 

For patients with hepatitis B or C, transaminases should be measured prior to initiation of ARV therapy and monitored monthly for the first 3 months after initiation of ARV therapy in HIV/HBV or HIV/HCV co-infected patients. Any transaminase elevation that is associated with jaundice or elevated bilirubin levels or loss of synthetic function in these patients (e.g., elevated PT/INR or decreased albumin) should be evaluated in conjunction with a hepatologist.

References:
  1. Acosta RD, Mays BC, Wong RK. Electronic clinical challenges and images in GI. CMV colitis with immune reconstitution syndrome. Gastroenterology 2008;134:e1-e2. [PubMed]
  2. von Both U, Laffer R, Grube C, et al. Acute cytomegalovirus colitis presenting during primary HIV infection: An unusual case of an immune reconstitution inflammatory syndrome. Clin Infect Dis 2008;46:e38-e40. [PubMed]

Management and Treatment

August 2009

RECOMMENDATIONS
  • Clinicians should initiate symptomatic treatment and supportive care for patients with IRIS. In severe cases, clinicians should consider prescribing prednisone 1-2 mg/kg or equivalent for 1-2 weeks, followed by a taper. (AIII)
  • Clinicians should closely monitor patients receiving corticosteroids for the development of opportunistic infections, including CMV retinitis and TB disease. (AIII)
  • Except in severe cases, ARV therapy should not be interrupted in patients with IRIS. (AIII)

Whenever IRIS is suspected, initial efforts should be focused on diagnosing and appropriately treating the OI, either previously known or unmasked by IRIS. IRIS resolves over time in most patients, and if not severe, symptomatic treatment and supportive care is often sufficient.

Management and Treatment of Mild IRIS

Nonsteroidal anti-inflammatory agents can be used for cases in which mild inflammation or fevers cause patients discomfort. When minor IRIS presentations occur, clinicians can reassure patients that these are an indication of immune reconstitution rather than progression of HIV disease and will resolve with standard treatment. In addition to standard therapy for the offending OI, the following treatments may alleviate inflammation in patients with mild IRIS:

  • Abscesses may be drained
  • Inflamed and painful lymph nodes may be excised
  • Inhaled steroids may alleviate mild pulmonary inflammation that cause bronchospasm or cough

Management and Treatment of Severe IRIS

Severe IRIS may threaten a patient’s functional status or may cause permanent disability. Examples of this are a decline in pulmonary capacity from TB or MAC, neurologic complications from cryptococcus, or vision loss from CMV.

Corticosteroid therapy to suppress inflammatory response is the most commonly used intervention in cases of severe IRIS. In a series of eight patients with severe TB-IRIS who were treated with 10 to 80 mg of prednisone daily, all patients improved. The median time to improvement was 3 days [1]. In nine patients with MAC-IRIS, eight responded to prednisone [2]. No trials on which to base a recommended dose of corticosteroids have been conducted, but some experts recommend 1-2 mg/kg prednisone, or the equivalent, for 1-2 weeks, then taper.

The risks of corticosteroid therapy should be weighed against the severity of the IRIS manifestations and the potential benefits, particularly given the high prevalence of diabetes mellitus, hypertension, and mental health disorders among HIV-infected patients. Risks of corticosteroid therapy include:

  • Hyperglycemia
  • Hypertension
  • Mental status changes
  • Worsening of an existing infection
  • Predisposition to a new infection

Improvement in life-threatening cases of IRIS after combination ARV therapy is discontinued has been reported; however, except in severe cases, ARV therapy should not be interrupted in patients with IRIS. Risks of stopping combination ARV therapy include HIV resistance, acquisition of new OIs, and recurrence of IRIS when therapy is later restarted.

In cases of cryptococcal-IRIS with worsening meningitis symptoms, therapeutic lumbar puncture to lower intracranial pressure, much like in acute cryptococcal meningitis, has been used.

Treatment of CMV vitritis with intraocular steroids has been described [3] but has not been useful in uveitis.

References:
  1. Breen RA, Smith CJ, Bettinson H, et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection.Thorax 2004;59:704-707. [PubMed]
  2. Phillips P, Bonner S, Gataric N, et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: Spectrum of disease and long-term follow-up. Clin Infect Dis 2005;41:1483-1497. [PubMed]
  3. Schrier RD, Song MK, Smith IL, et al. Intraocular viral and immune pathogenesis of immune recovery uveitis in patients with healed cytomegalovirus retinitis. Retina 2006;26:165-169. [PubMed]

All Recommendations

Medical Care Criteria Committee, August 2009

ALL RECOMMENDATIONS: IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS)
When to Initiate ART in Patients with Recent OIs 
  • Clinicians should strongly recommend that patients recovering from acute OIs initiate ARV therapy as soon as tolerability has been established and the potential for drug-drug interactions has been minimized (see Antiretroviral Therapy).
Presentation and Diagnosis 
  • Clinicians should consider IRIS when inflammatory signs or symptoms occur after recent initiation, re-initiation, or change to a more effective combination ARV therapy with associated increase in CD4 cell count and/or decrease in viral load and the following have been excluded:
    • Worsening of known infections due to inadequate or inappropriate therapy (AIII)
    • New infections not known to be associated with IRIS (e.g., bacterial sepsis) (AIII)
    • Medication reaction (AIII)
Preventing Complications 
  • Clinicians should be alert to the possibility of IRIS as CD4 cell counts are restored after initiation of ARV therapy. (AIII)
  • After initiation of ARV therapy, HIV-infected patients with a history of CMV retinitis should be monitored for possible IRIS by dilated ophthalmologic examination:
    • Every 3 months for the first year after initiation of ARV therapy (AIII)
    • Immediately if there is a change in visual acuity or development of floaters (AIII)
  • For HIV-infected patients who are co-infected with hepatitis B or C, clinicians should measure transaminase levels:
    • Before initiation of ARV therapy (AI)
    • Monthly for the first 3 months after initiation of ARV therapy to monitor for possible immune reconstitution inflammatory syndrome (AIII)
Management and Treatment 
  • Clinicians should initiate symptomatic treatment and supportive care for patients with IRIS. In severe cases, clinicians should consider prescribing prednisone 1-2 mg/kg or equivalent for 1-2 weeks, followed by a taper. (AIII)
  • Clinicians should closely monitor patients receiving corticosteroids for the development of opportunistic infections, including CMV retinitis and TB disease. (AIII)
  • Except in severe cases, ARV therapy should not be interrupted in patients with IRIS. (AIII)

Antiretroviral Therapy Guideline

Initiating ART

Medical Care Criteria Committee, April 2015

Antiretroviral therapy (ART) refers to the use of pharmacologic agents that have specific inhibitory effects on HIV replication. The use of less than three active agents is not recommended for initiating treatment. These agents belong to six distinct classes of drugs: the nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs, NtRTIs), the non-nucleoside reverse transcriptase inhibitors (NNRTIs), the protease inhibitors (PIs), the fusion inhibitors (FIs), the CCR5 co-receptor antagonists, and the integrase strand transfer inhibitors (INSTIs). See all commercially available antiretroviral drugs that are FDA-approved for the treatment of HIV/AIDS.

Goals, Benefits, and Risks of ART

April 2015

RECOMMENDATIONS
  • Clinicians should prescribe an antiretroviral (ART) regimen that is best able to delay disease progression, prolong survival, and maintain quality of life through maximal viral suppression (see text). (I)
  • The clinician should involve the patient in the decision-making process when determining whether to implement ART. The clinician should review the benefits and risks of treatment for each individual patient. (III)

Goals of ART:

  • Maximal and durable suppression of viral replication (measured by viral load assays)
  • Restoration and/or preservation of immune function
  • Reduced HIV-related morbidity and mortality
  • Improved quality of life
  • Limitation of the likelihood of viral resistance to preserve future treatment option

In typical clinical practice, durable suppression of viral replication to undetectable levels may be achieved in approximately 80% of cases. The maximal suppression of viral replication is generally associated with gradual increases in the CD4 count and clinical stabilization or improvement of HIV-associated symptoms. When maximal suppression is not attainable due to the inability to construct an effective regimen for the patient, partial viral suppression (≥0.5 log reduction, or 3-fold, from baseline viral load value) and stable CD4 counts are reasonable alternative goals. However, incomplete suppression of viral replication may be associated with continued immunologic and clinical deterioration and the evolution of additional resistance mutations. Patients who are unable to adhere strictly to complex medication regimens are those most likely to develop HIV-drug resistance and to face limited future ART options. The clinician needs to review the benefits and risks of treatment for each individual patient (see below).

Benefits of ART:

  • The preservation and/or restoration of immune function
  • Improvement of overall health and the prolongation of life
  • The suppression of viral replication
  • The possible decrease in risk of viral transmission to others (including fetal transmission)

Risks of ART:

  • Adverse effects of the medications on quality of life
  • Known, and as yet unknown, long-term drug toxicities, including potential fetal toxicity
  • The development of HIV drug resistance to drugs currently available and possibly to those not yet available, which may limit future treatment options

When to Initiate ART

June 2016

RECOMMENDATIONS 
  • ART should be recommended for all patients with a diagnosis of HIV infection. (AI)
  • Clinicians should strongly recommend initiation of ART for patients who present with any of the following conditions that increase the urgency of starting ART:
    • AIDS-defining condition (AI)
    • Pregnancy [a] (AI)
    • Symptomatic from HIV, including any of the following:
      • HIV-associated neurocognitive disorder (HAND) [b] (AII)
      • Severe thrombocytopenia (AII)
      • HIV-associated nephropathy (AII)
      • HIV-related malignancies (AII)
    • Chronic hepatitis B or C infection [c,d] (AII)
    • Age 50 or older (AII)
  • Patients with seronegative partners should be counseled about the reduction of HIV transmission risk when effective ART is initiated and viral suppression is achieved; ART is strongly recommended in patients with seronegative partners. (AI)
  • Decisions to initiate ART should be individualized, particularly for the following populations:
    • Long-term nonprogressors [e] (AII)
    • Elite controllers [f] (AIII)
    • Patients with potential barriers to adherence (AIII)
  • Evaluation and preparation for ART initiation includes each of the following essential components:
    • Discussion with the patient about risks and benefits of ART (AIII) (see Counseling and Education Before Initiating ART)
    • Assessment of patient readiness (AIII)
    • Identification and amelioration of factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders (AII)
  • Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (AIII)
  • Clinicians should involve patients in the decision-making process regarding initiation of ART. The patient should make the final decision of whether and when to initiate ART. (AIII)
  • When the decision to initiate treatment is made, ART should be prescribed and monitored by, or in consultation with, clinicians who have experience in managing ART. (AII)

Notes:

  1. For recommendations on initiating ART in HIV-infected pregnant women, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.
  2. HAND is currently used to encompass a hierarchy of progressive patterns of central nervous system involvement ranging from asymptomatic neurocognitive impairment (ANI), to minor neurocognitive disorder (MND), to the more severe HIV-associated dementia (HAD) (see Cognitive Disorders Guideline).
  3. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B (see HBV-HIV Coinfection guideline).
  4. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.
  5. Long-term nonprogressors demonstrate a lack of disease progression, marked by no symptoms and low viral loads in the absence of therapy during long-term follow-up. Most published studies of long-term nonprogressors include 7-10 years of follow-up.
  6. Elite controllers suppress HIV to low but detectable levels (see Deferring ART, below).

Preliminary results from the START trial [1] and increasingly strong cohort data show that untreated HIV infection leads to increased morbidity and mortality from both HIV-related and non-HIV-related conditions, even at high CD4 counts. Together with the dramatic reduction of transmission risk with effective treatment, these data support the initiation of ART regardless of CD4 count in all adequately prepared patients, including patients diagnosed with acute HIV infection (for more discussion see Diagnosis and Management of Acute Infection). Patients in care who are documented long-term nonprogressors or elite controllers are a group that may warrant special consideration (see Deferring ART). Patients with chronic infection and higher CD4 counts are at low risk for short-term adverse outcomes, allowing time for proper assessment, education, and engagement of the patient in the decision to treat.

In START, a randomized trial initiating ART in treatment-naïve patients with CD4 counts >500 cells/mm3 versus waiting for a decrease to ≤350 cells/mm3 before initiation showed a 53% reduction in serious illness and death in the early ART group [1]. Data from NA-ACCORD, a large observational cohort study, showed that both morbidity and mortality were improved by initiation of ART in patients with CD4 counts in the high or even normal range [2]. A significantly decreased risk of death was observed in patients who initiated therapy at CD4 counts >500 cells/mm3 compared to those who deferred to <500 cells/mm3, as well as in the cohort who initiated ART in the 350-500 cells/mm3 range compared with those deferring to <350 cells/mm3 [2]. Although other cohort studies demonstrated only a minimal survival advantage [3] or no survival advantage among those starting ART at the highest CD4 counts, they did confirm the benefits of initiating ART at levels ≤500 cells/mm3 [4-6]. Another showed an approximately 33% reduction in the risk of death from end-stage liver disease, non-AIDS infections, and non-AIDS-defining cancers with each 100 cells/mm3 increase in CD4 count [7]. A randomized study of early versus deferred therapy in patients with CD4 counts in the 350-550 cells/mm3 range showed no mortality benefit [8]; however, this study has significant limitations, most notably a relatively brief follow-up period.

Accumulating evidence suggests that patients who initiate ART earlier or spend less cumulative time with detectable plasma viremia are less likely to suffer certain complications, such as cardiovascular disease [7,9-12], neurocognitive dysfunction [13-16], decreased risk of severe bacterial infections [17], and some non-HIV-related malignancies [18-21]. Cohort data also demonstrate that although older patients are likely to achieve virologic suppression, they are less likely to achieve an immunologic response, as measured by an increase of CD4 count by 100 cells/mm3, and that patients >55 years old may be at higher clinical risk even after starting therapy [22]. The poor immunologic recovery seen in older patients is associated with higher morbidity and mortality, particularly cardiovascular events [23]. In one study, men ≥50 years of age who initiated ART with CD4 counts in the 351-500 cells/mm3 range were able to achieve similar immunologic responses as younger men who initiated at lower CD4 counts [24].

Studies have shown that, for HIV-infected pregnant women, the administration of ART during pregnancy and/or intrapartum significantly reduces the risk of mother-to-child transmission (MTCT) of HIV [25,26]. In addition, a large study showed a 96% reduction in transmission between serodiscordant heterosexual couples when the positive partner was receiving ART [8], adding to the body of evidence that lower viral load reduces transmission risk. ART is now part of the established strategy aimed at reducing HIV transmission and is an essential component of prevention interventions along with risk-reduction counseling, safer-sex practices, and avoidance of needle-sharing. Although the majority of patients both in New York and worldwide present later in the course of their HIV infection [27-29], ongoing efforts to offer universal HIV testing to all patients over age 13 may begin to identify patients earlier in their disease who can benefit from immediate treatment.

KEY POINT
  • For HIV therapy to be successful over time, the initiation of ART should involve both the selection of the most appropriate regimen and the acceptance of the regimen by the patient, bolstered by education and adherence counseling. All are critical in achieving the goal of durable and complete viral suppression.
RESOURCES
The CEI Line provides primary care providers in New York State the opportunity to consult with clinicians who have experience managing ART. The CEI Line can be reached at 1-866-637-2342 or 1-585-273-2793.The AIDS Institute maintains a voluntary HIV Provider Directory to assist with identification of experienced providers in New York State. Experienced providers can also be identified through the American Academy of HIV Medicine (AAHIVM) and the HIV Medicine Association (HIVMA).

Counseling and Education Before Initiating ART

RECOMMENDATIONS
  • Counseling and education should include the following:
    • Basic education about HIV, CD4 cells, viral load, and resistance (AIII)
    • Available treatment options and potential risks and benefits of therapy (AIII) (see text)
    • The need for strict adherence to avoid the development of viral drug resistance (AII) 
    • Use of safer-sex practices and avoidance of needle-sharing activity, regardless of viral load, to prevent HIV transmission or superinfection (AIII)
  • Clinicians should involve the patient in the decision-making process regarding initiation of ART. (AIII)

Discussion of ART should occur at the start of care for all HIV-infected patients, regardless of CD4 count. The clinician and patient should discuss the benefits of early ART (see below) and individual factors that may affect the decision to initiate, such as patient readiness or reluctance and adherence barriers. Clinicians should involve the patient in the decision-making process regarding initiation of ART [30]. When clinicians and patients engage in shared decision-making, patients are more likely to choose to initiate ART and to achieve an undetectable viral load [31]. Misconceptions about treatment initiation should be addressed, including the implication that starting ART represents advanced HIV illness. Initiating ART before symptoms occur allows patients to stay healthier and live longer.

RESOURCES
Patients who do not have health insurance may qualify for Medicaid or the NYSDOH HIV Uninsured Care Program, which provides access to free health care (HIV drugs, primary care, home care, and the ADAP Plus Insurance Continuation Program, or APIC) for residents who are HIV-infected but uninsured or underinsured. The program is open Monday-Friday, 8:00AM-5:00PM and can be reached: in state 1-800-542-2437; out-of-state 1-518-459-1641; TDD 1-518-459-0121.If eligible, patients may also consider treatment options through enrollment in clinical trials. A resource that may help with this process is the AIDS Clinical Trials Information Service (1-800-TRIALS-A).

The risks and benefits of early ART to discuss with patients when making the decision of whether and when to initiate ART are outlined below.

BENEFITS of early ART in asymptomatic patients: 
(early therapy = initiation at CD4 counts >500 cells/mm3)

  • Earlier treatment reduces both HIV-related and non-HIV-related morbidity and mortality [1,2,7,10,18,32-35]
  • Delay or prevention of immune system compromise [36]
  • Possible lower risk of antiretroviral resistance [37]
  • Decreased risk of sexual transmission of HIV [8,38-40] (The risk of viral transmission still exists even when the plasma viral load is undetectable; ART is not a substitute for primary HIV prevention measures, such as avoiding needle sharing, practicing safer sex [46].)
  • Decreased risk of several severe bacterial infections [17]

DISADVANTAGES of early ART in asymptomatic patients:

  • Potential drug-related reduction in quality of life in otherwise asymptomatic individuals [41-43]
  • Possibility of greater cumulative side effects from ART [44]
  • Possibility for earlier development of drug resistance and limitation in future [45] antiretroviral options if adherence and viral suppression are suboptimal
  • Possibility for earlier onset of treatment fatigue
  • Higher prescription drug costs for the individual

Deferring ART

RECOMMENDATION
  • In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support (see NYSDOH Linkage, Retention, and Treatment Adherence Initiative). (AII)
  • Except in cases when initiation of treatment is urgent (see Initiating ART Following Acute Opportunistic Infections, below), clinicians should educate and prepare patients before initiating ART in those with potential barriers to adherence, including active alcohol or drug use; lack of insurance, transportation, or housing; depression; mistrust of medical providers; or a poor social support system. (AIII)

Potential Barriers to Adherence

Although the current first-line regimens used for ART are much easier to tolerate with fewer side effects than earlier combinations, they are not free of side effects. Their use requires a lifelong commitment from the patient. Patients who prefer not to take medication, or who do not understand the significance of skipping doses, are at high risk for poor adherence and subsequent viral resistance. Except when initiation of treatment is clinically urgent, more than one visit before initiating ART is advisable to ensure adequate understanding of the importance of adherence and to address potential barriers or impediments to therapy. These may include but are not limited to active alcohol or drug use; lack of insurance, transportation, or housing; depression; mistrust of medical providers; or a poor social support system. These barriers should not necessarily preclude initiation of ART; some may not be completely modifiable before starting therapy and will require ongoing attention and use of supportive services throughout the course of therapy.

Patients who are at high risk for poor adherence may benefit if initiation of ART is temporarily deferred while further patient education efforts are undertaken. In these patients, the risk of viral resistance and eventual treatment failure may outweigh any clinical benefit from earlier treatment before strict adherence can be expected [46]. These patients should remain under particularly close observation for clinical and laboratory signs of disease progression [47]. ART should be initiated as soon as the patient seems prepared to adhere to a treatment regimen. In patients with advanced AIDS, it is appropriate to initiate ART even if some barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support.

Long-term Nonprogressors and Elite Controllers

RECOMMENDATIONS
  • Decisions to initiate ART in long-term nonprogressors (AII) and elite controllers (AIII) should be individualized.
  • Clinicians should consult with a provider experienced in the management of ART when considering whether to initiate ART in long-term nonprogressors and elite controllers. (AIII)
  • Long-term nonprogressors demonstrate a lack of disease progression, marked by no symptoms and low viral loads in the absence of therapy during long-term follow-up. Most published studies of long-term nonprogressors include 7-10 years of follow-up. [48]
  • Elite controllers suppress HIV to low but detectable levels (<50-75 copies/mL) for many years. [48]

The role of early ART initiation in long-term nonprogressors or elite controllers is unclear. At this time, there are not enough data to recommend for or against initiation of ART in long-term nonprogressors and elite controllers. Close monitoring of CD4 count and viral load level may be an acceptable approach. Declines in CD4 count should prompt consideration of initiation of ART. Elite controllers have demonstrated CD4 cell increases after initiation of ART [49]. Another study found higher rates of hospitalizations in elite controllers compared to treatment suppressed patients, particularly for cardiovascular and psychiatric conditions [50]; however, there were important limitations in this analysis and it does not provide definitive evidence in favor of treating this rare population based on current information [51]. The clinician and patient should discuss the current data on the risks and benefits of early ART as well as individual factors that may affect the decision to initiate, such as patient readiness and reluctance, adherence barriers, CD4 cell count and viral load, comorbidities, age, and partner serodiscordance. If treatment is delayed, clinicians should counsel patients about the risk of HIV transmission to partners.

Initiating ART Following Acute Opportunistic Infections

RECOMMENDATIONS
  • Clinicians should recommend that patients beginning treatment for acute opportunistic infections (OIs) initiate ART within 2 weeks of OI diagnosis (see next recommendation for exceptions). (AI)
  • Clinicians should not immediately initiate ART in patients with tuberculous meningitis or cryptococcal meningitis. (AI)
  • Consultation with a clinician with experience in management of ART in the setting of acute OIs is recommended. (AIII)
  • For all other manifestations of tuberculosis (TB), clinicians should initiate ART in HIV-infected patients as follows:
    • For patients with CD4 counts ≥50 cells/mm3: as soon as they are tolerating anti-TB therapy and no later than 8-12 weeks after initiating anti-TB therapy (AI)
    • For patients with CD4 counts <50 cells/mm3: within 2 weeks of initiating anti-TB therapy (AI)

In a randomized study, patients who initiated ART at a median of 12 days from start of OI therapy had better outcomes, as measured by disease progression and death, without an increase in adverse events, compared to those who initiated ART at a median of 45 days from presentation [52]. Although this study excluded patients with active TB, three randomized controlled trials in patients newly diagnosed with HIV and pulmonary TB have demonstrated a significant mortality benefit when ART was initiated during the first 2 months of starting anti-TB therapy and a further benefit when those who were severely immunocompromised initiated therapy in the first 2 weeks [53-55]. Although antiretroviral agents and anti-TB medications can have overlapping toxicities, ART should be initiated within the first 8 to 12 weeks of starting anti-TB therapy. Patients with CD4 counts <50 cells/mm3 should receive ART within the first 2 weeks of initiating anti-TB therapy.

Tuberculous meningitis and cryptococcal meningitis are exceptions; there are data showing that early initiation of ART increases adverse events and mortality in this setting [56-60]. Close attention should be paid to possible drug-drug interactions between OI therapy and ART. In some cases, determining the optimal timing for initiating ART in patients with OIs can be complex and may require consultation with a clinician with experience in management of ART in this context.

After initiating ART, clinicians need to be alert to the possibility of immune reconstitution syndromes as CD4 cell counts are restored (see Immune Reconstitution Inflammatory Syndrome).

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All Recommendations: Initiating ART

Medical Care Criteria Committee, September 2015

ALL RECOMMENDATIONS: INITIATING ART
Goals, Benefits, and Risks 
  • Clinicians should prescribe an ART regimen that is best able to delay disease progression, prolong survival, and maintain quality of life through maximal viral suppression (see text). (I)
  • The clinician should involve the patient in the decision-making process when determining whether to implement ART. The clinician should review the benefits and risks of treatment for each individual patient. (III)
When to Initiate 
  • ART should be recommended for all patients with a diagnosis of HIV infection. (AI)
  • Clinicians should strongly recommend initiation of ART for patients who present with any of the following conditions that increase the urgency of starting ART:
    • AIDS-defining condition (AI)
    • Pregnancy [a] (AI)
    • Symptomatic from HIV, including any of the following:
      • HIV-associated neurocognitive disorder (HAND) [b] (AII)
      • Severe thrombocytopenia (AII)
      • HIV-associated nephropathy (AII)
      • HIV-related malignancies (AII)
    • Chronic hepatitis B or C infection [c,d] (AII)
    • Age 50 or older (AII)
  • Patients with seronegative partners should be counseled about the reduction of HIV transmission risk when effective ART is initiated and viral suppression is achieved; ART is strongly recommended in patients with seronegative partners. (AI)
  • Decisions to initiate ART should be individualized, particularly for the following populations:
    • Long-term nonprogressors [e] (AII)
    • Elite controllers [f] (AIII)
    • Patients with potential barriers to adherence (AIII)
  • Evaluation and preparation for ART initiation includes each of the following essential components:
    • Discussion with the patient about risks and benefits of ART (AIII) (see Counseling and Education Before Initiating ART)
    • Assessment of patient readiness (AIII)
    • Identification and amelioration of factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders (AII)
  • Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (AIII)
  • Clinicians should involve patients in the decision-making process regarding initiation of ART. The patient should make the final decision of whether and when to initiate ART. (AIII)
  • When the decision to initiate treatment is made, ART should be prescribed and monitored by, or in consultation with, clinicians who have experience in managing ART. (AII)
Counseling and Education before ART Initiation 
  •  Counseling and education should include the following:
    • Basic education about HIV, CD4 cells, viral load, and resistance (AIII)
    • Available treatment options and potential risks and benefits of therapy (AIII) (see text)
    • The need for strict adherence to avoid the development of viral drug resistance (AII) (see Adherence)
    • Use of safer-sex practices and avoidance of needle-sharing activity, regardless of viral load, to prevent HIV transmission or superinfection (AIII)
  • Clinicians should involve the patient in the decision-making process regarding initiation of ART. (AIII)
Deferring ART 
  • In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support (see NYSDOH Linkage, Retention, and Treatment Adherence Initiative). (AII)
  • Except in cases when initiation of treatment is urgent (see Initiating ART Following Acute Opportunistic Infections), clinicians should educate and prepare patients before initiating ART in those with potential barriers to adherence, including active alcohol or drug use; lack of insurance, transportation, or housing; depression; mistrust of medical providers; or a poor social support system. (AIII)
  • Decisions to initiate ART in long-term nonprogressors (AII) and elite controllers (AIII) should be individualized.
  • Clinicians should consult with a provider experienced in the management of ART when considering whether to initiate ART in long-term nonprogressors and elite controllers. (AIII)
Initiating ART Following Acute OIs
  • Clinicians should recommend that patients beginning treatment for acute opportunistic infections (OIs) initiate ART within 2 weeks of OI diagnosis (see next recommendation for exceptions). (AI)
  • Clinicians should not immediately initiate ART in patients with tuberculous meningitis or cryptococcal meningitis. (AI)
  • Consultation with a clinician with experience in management of ART in the setting of acute OIs is recommended. (AIII)
  • For all other manifestations of tuberculosis (TB), clinicians should initiate ART in HIV-infected patients as follows:
    • For patients with CD4 counts ≥50 cells/mm3: as soon as they are tolerating anti-TB therapy and no later than 8-12 weeks after initiating anti-TB therapy (AI)
    • For patients with CD4 counts 3: within 2 weeks of initiating anti-TB therapy (AI)

Notes

  1. For recommendations on initiating ART in HIV-infected pregnant women, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.

  2. HAND is currently used to encompass a hierarchy of progressive patterns of central nervous system involvement ranging from asymptomatic neurocognitive impairment (ANI), to minor neurocognitive disorder (MND), to the more severe HIV-associated dementia (HAD) (see Cognitive Disorders Guideline).

  3. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B (see Hepatitis B Virus guideline).

  4. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.

  5. Long-term nonprogressors demonstrate a lack of disease progression, marked by no symptoms and low viral loads in the absence of therapy during long-term follow-up. Most published studies of long-term nonprogressors include 7-10 years of follow-up.

  6. Elite controllers suppress HIV to low but detectable levels.

Monitoring Patients on ART Guideline

Virologic and Immunologic Monitoring

Medical Care Criteria Committee, June 2016

Periodic laboratory tests are necessary to evaluate the response to ART and its potential related side effects. In the setting of ART failure, viral resistance assays should be used.

HIV RNA AS MEASURE OF EFFECTIVE ART
  • Quarterly CD4 count monitoring is no longer recommended for non-pregnant patients receiving ART who have consistently undetectable HIV RNA levels and CD4 counts >200 cells/mm3 (see Table 1 for recommended intervals). (AII)
  • Regular monitoring of HIV RNA levels remains the most accurate and meaningful measure of effective ART (see Table 1 for recommended intervals). (AI)

Regular monitoring of CD4 counts in patients with consistently undetectable HIV viral loads and CD4 counts >200 cells/mm3 offers little utility in clinical practice today. Clinicians rarely use this information to guide decision-making for clinically stable, virologically suppressed patients. Monitoring of HIV RNA levels to confirm appropriate response to treatment and durable viral suppression is the most accurate and meaningful measure of the effectiveness of ART [1].

RECOMMENDATIONS
  • Clinicians should monitor HIV RNA levels and CD4 counts according to the recommended intervals in Table 1. Follow-up visits should be scheduled more frequently as clinically necessary to address non-HIV-related conditions, secondary prevention, and issues that may affect adherence to ART or retention in care, such as substance use, mental health disorders, unstable housing, or need for supportive services. (AIII)
  • Clinicians should assess response to ART using viral load assays. (AI)
  • CD4 cell counts should not be used for diagnosis of HIV infection. (AI)

Very few studies address the appropriate frequency of viral load monitoring. A recent retrospective study noted that the strongest predictor of virologic failure at 12 months was a missed or cancelled appointment rather than the interval of follow-up [2]. However, this and other similar studies [3,4] have significant limitations, including their retrospective nature and short follow-up periods. Until more definitive data are available, the decision to lengthen monitoring intervals for HIV RNA level should be individualized. Patients who are monitored at longer intervals should be carefully selected based on length of viral suppression, CD4 count, and adherence to medical care, including visit attendance and retention in care.

KEY POINT
  • Quarterly HIV RNA monitoring remains appropriate for patients with a recent history of non-adherence, mental health disorders, substance use, homelessness, poor social support system, or other major medical conditions. Semiannual monitoring may be appropriate for patients with persistently undetectable HIV RNA and none of the above characteristics.

Table 1 provides a guide for monitoring HIV RNA levels and CD4 counts.

Table 1: Virologic and Immunologic Monitoring for Non-Pregnant Patients [a]
At Baseline HIV RNA Levels (copies/mL) CD4 Lymphocyte Count (cells/mm3)

All patients

  • Yes (AI)
  • Yes (AI)
Treatment Monitoring HIV RNA Levels (copies/mL) CD4 Lymphocyte Count (cells/mm3)

Following (1) initiation of ART or (2) a change in ART regimen after virologic failure [b] with new resistance to prior ART

  • Within 4 weeks of initiation of ART or change in regimen (AIII)
  • At least every 8 weeks until complete suppression [c] is documented (AIII)
  • Repeat at 12 weeks and then every 4 months until CD4 >200 cells/mm3 on two measurements obtained at least 4 months apart (AII); then monitor as below once suppressed

Following a change in ART to simplify treatment regimen or reduce toxicity for patients with suppressed virus

  • Within 4 weeks after change in regimen to ensure continued suppression (AIII); then monitor as below for suppressed
  • Monitor as below for suppressed

Patients on ART who achieve complete suppression [c]

  • At least every 4 months after complete suppression (AIII)
  • May extend intervals to every 6 months in selected stable patients with CD4 counts >200 cells/mm3 after 1 year of complete suppression [2] (BII)
  • If CD4 ≤300 cells/mm3: At least every 6 months (BIII)
  • If CD4 >300 to ≤500 cells/mm3: At least every 12 months (BII)
  • If CD4 >500 cells/mm3: further monitoring is optional (BIII)

Patients on previously suppressive ART with new HIV RNA [d] above the lower limit of detection using a highly sensitive assay [c]

All patients:

  • Assess adherence (AIII)
  • Assess for drug-drug interactions (AIII)

Viral load ≥500 copies/mL:

  • Have patient return within 2 weeks and:
    • Repeat viral load (AII) and obtain resistance testing (AI)
    • Obtain CD4 count if not done within previous 6 months (BIII)

Viral load <500 copies/mL:

  • Repeat viral load test within 4 weeks to differentiate low level transient viremia (“blip”) from virologic failure [b,e]. (AII)
  • If viral load remains detectable on repeat test:
    • Obtain CD4 count if not done within previous 6 months (BIII)
    • Consider resistance testing [f] (BIII)

Patients not on ART: According to NYSDOH recommendations, ART is recommended for all HIV-infected patients [g]

  • If CD4 ≤500 cells/mm3: At least every 4 months (AIII)
  • If CD4 >500 cells/mm3: At least every 6 months (AIII)
  • Continue to discuss ART initiation (AI)
  • If CD4 ≤500 cells/mm3: At least every 4 months (AIII)
  • If CD4 >500 cells/mm3: At least every 6 months (AIII)
  • Continue to discuss ART initiation (AI)
Notes:

  1. For monitoring HIV RNA levels and CD4 counts in HIV-infected pregnant women, see the DHHS Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.
  2. Virologic failure is defined as the inability to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL [5].
  3. Complete suppression is generally considered below the lower limit of detection of a highly sensitive assay (<20 to <50 copies/mL).
  4. Patients with repeated intermittent low level viremia ≤200 copies/mL over a period of years without demonstrated failure may continue routine testing intervals.
  5. ART should not be changed based on a single viral load elevation. The risk of virologic rebound (breakthrough) increases when values are >500 copies/mL [6].
  6. Standard genotypic tests may not provide resistance results when viral load is low. For repeated low-level viremia, an assay that detects resistance mutations in archived proviral DNA is available; however, clinical data are insufficient to recommend for or against its use in the patient care setting.
  7. See When to Initiate ART.

Plasma HIV-1 RNA Level (Viral Load)

Plasma levels of viral RNA have been shown to correlate with clinical outcome, including overall mortality, and measurement of HIV RNA levels provides the most precise means of establishing whether a response to ART has occurred [7-11]. HIV RNA levels should be obtained from all patients at baseline [12-17].

For patients beginning ART, or those changing therapy as a result of virologic failure, HIV RNA should be measured at 4 weeks after initiation of therapy and should decrease by at least 1 log (10-fold) in the presence of effective therapy [18] (see Table 3). For patients who do not have background antiretroviral resistance, an undetectable viral load (<50 copies/mL) is usually achieved within 3 months. Patients with a baseline HIV viral load >100,000 copies/mL can be expected to achieve an undetectable viral load within 6 months of effective treatment.

An absent or incomplete response of viral load to ART should raise concerns about poor adherence to therapy and/or viral resistance [19,20].

Patients on previously suppressive ART with newly detectable HIV RNA levels of 50 to 500 copies/mL may be experiencing low-level transient viremia (“blip”) and not virologic failure. A blip by definition means that the viral load is again below the level of quantification on repeat testing performed promptly after a detectable result in someone previously suppressed. Persistent elevation, even at low levels, warrants further investigation. Acute concurrent illness and/or recent vaccination may cause this transient rise; however, studies have suggested that low-level transient viremia represents random biologic and statistical variation or false elevations of viral load resulting from laboratory processing [21,22]. Blips are not known to be associated with the development of resistance mutations or virologic failure and do not require a change in ART [22]. Retesting should be performed within 4 weeks to differentiate low-level transient viremia (a blip) from sustained viremia and possible virologic failure. The risk of virologic rebound (breakthrough) increases when values are >500 copies/mL [6]. However, ART should not be changed based on a single viral load elevation.

Advances in molecular detection technology have led to the development of HIV nucleic acid tests (NATs) that are highly sensitive and more reliable than earlier versions. Real-time polymerase chain reaction (PCR) technology has been widely adopted for HIV-1 RNA quantification, but new technologies are continually emerging and being adapted to viral detection and quantification. The currently available HIV-1 viral load tests that use real-time PCR technology offer larger dynamic range of quantification than early-version viral load tests. The lower and upper limits of quantification of the currently available FDA-approved HIV-1 viral load tests are shown in Table 2. Several different HIV viral load tests have been developed, and four are currently approved for use in the United States.

Table 2: FDA-Approved Quantitative HIV-1 RNA Assays for Viral Load Monitoring
Test Name Method

Lower and Upper Limits of Quantification (LOQ)

Abbott RealTime HIV-1  (Abbott Laboratories)

Real-time PCR
  • 40* copies/mL
  • 10,000,000 copies/mL

Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, version 2.0 (Roche Diagnostics)

Real-time PCR
  • 20 copies/mL
  • 10,000,000 copies/mL

Cobas HIV-1 quantitative NAT for use on Cobas 6800/8800 systems (Roche Diagnostics)

Real-time PCR
  • 20 copies/mL
  • 10,000,000 copies/mL

Cobas TaqMan HIV-1 Test, v2.0 for use with the high pure system (Roche Diagnostics)

Real-time PCR
  • 34 copies/mL
  • 10,000,000 copies/mL

*This lower LOQ applies when 1.0 mL of plasma is used. When 0.5 mL and 0.2 mL of plasma are used, the lower LOQ is 75 copies/mL and 150 copies/mL, respectively.

All of the current FDA-approved viral load assays quantify the level of cell-free virus in an individual’s plasma and are approved for monitoring response to ART, tracking viral suppression, and detecting treatment failure. Successful ART should decrease viral load 1.5 to 2 logs (30- to 100-fold) within 6 weeks, with the viral load decreasing below the limit of detection within 6 months [23]. Cohort studies strongly suggest that patients with viral loads <50 copies/mL have more sustained viral suppression than patients with viral loads between 50 and 400 copies/mL. Assays that can detect <50 copies/mL are recommended for determining prolonged viral suppression and for monitoring patients who are on ART.

KEY POINT
  • Achieving and maintaining an undetectable viral load is always the goal of ART.

Lymphocyte Subsets (CD4 Cell Count)

CD4 lymphocyte count is used to evaluate immunologic staging, predict the risk of clinical progression, and make decisions regarding prophylaxis of opportunistic infections [24,25]. Low CD4 cell counts can be seen in other disease processes and should therefore not be used for diagnosis of HIV. Although, historically, CD4 cell count was used to establish a threshold for initiating ART, current guidelines in New York State recommend ART for all HIV-infected patients regardless of CD4 cell count. For patients who may not be ready to initiate ART, CD4 cell count can be used to guide discussions between patient and provider regarding the urgency of initiating ART.

Although CD4 counts should be obtained from patients at baseline [26-30], clinicians are unlikely to use CD4 counts to guide clinical decision-making in practice for virologically suppressed patients once their CD4 count remains above 200 cells/mm3. However, for persons infected with HIV-2 or HIV-1 variants that cannot be accurately quantified using viral load assays, CD4 count remains the most effective monitoring tool for progression of disease (see Human Immunodeficiency Virus Type-2).

Although a significant CD4 count increase often occurs among patients treated with effective ART, the absence of such an increase should not be interpreted as treatment failure if the viral load declines appropriately. ART regimens are generally not changed in patients with undetectable viral loads who experience immunologic failure, although patients should remain on appropriate prophylaxis for opportunistic infections based on CD4 count. Lack of correlation between viral load and CD4 cell response is particularly common among patients ≥50 years old [31,32] and patients with low initial CD4 cell counts (<100 cells/mm3) [26,33,34].

Absolute CD4 cell counts are calculated values that may fluctuate widely. The calculation is made by multiplying the total white blood cell count (in thousands) by the percentage of total lymphocytes and then by the percentage of CD4 lymphocytes. Therefore, any change in one of these three parameters will cause the absolute CD4 count to vary. CD4 percentage is a direct measurement and more reliable than the calculated absolute CD4 value, especially over time. A stable CD4 percentage, even in the setting of fluctuations in the absolute CD4 cell count, can reassure both the patient and the clinician that immunologic stability is present.

Some factors that can cause these fluctuations include sex, age, race, drugs (zidovudine, cephalosporins, cancer chemotherapy, nicotine, interferon, and corticosteroids), anti-lymphocyte antibodies, and splenectomy. Differences in reagents and equipment both within a laboratory and between laboratories may further contribute to variations in CD4 cell counts. There is also interlaboratory variation of normal range.

Table 3: Interpretation of Viral Load
HIV -1 RNA Copy Number
Copies/mm3 Log10
1,000,000
100,000
10,000
1,000
100
6.0
5.0
4.0
3.0
2.0
Reduction with ART if Patient has 100,000 copies/mm3
Log Change Percent Decrease Fold Reduction Resultant Copy Number
0.5 66.00 3 33,000
1.0 90.00 10 10,000
2.0 99.00 100 1,000
3.0 99.99 1,000 100
References:
  1. Gale HB, Giettermann SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >300 cells/mm3 and HIV-1 suppression? Clin Infect Dis 2013;56:1340-1343. [PubMed]
  2. Buscher A, Mugavero M, Westfall AO, et al. The association of clinical follow-up intervals in HIV-infected persons with viral suppression on subsequent viral suppression. AIDS Patient Care STDs 2013;27:459-466. [PubMed]
  3. Reekie J, Mocroft A, Sambatakou H, et al. Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure? AIDS 2008; 22:2381–2390. [PubMed]
  4. Romih V, Zidovec Lepej S, Gedike K, et al. Frequency of HIV-1 viral load monitoring of patients initially successfully treated with combination antiretroviral therapy. PLoS One 2010; 5:e15051. [PubMed]
  5. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed June 10, 2015. Available athttp://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
  6. Grennan JT, Loutfy MR, Su D, et al. Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: A recurrent events analysis. J Infect Dis 2012;205:1230-1238. [PubMed]
  7. Marschner IC, Collier AC, Coombs RW, et al. Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis 1998;177(1):40-7. [PubMed]
  8. HIV Surrogate Marker Collaborative Group. Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: a meta-analysis. AIDS Res Hum Retroviruses 2000;16(12):1123-33. [PubMed]
  9. Murray JS, Elashoff MR, Iacono-Connors LC, et al. The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs. AIDS1999;13(7):797-804. [PubMed]
  10. Mellors JW, Muñoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med1997;126(12):946-54. [PubMed]
  11. Thiébaut R, Morlat P, Jacqmin-Gadda H, et al. Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d’Epidémiologie du SIDA en Aquitaine (GECSA). AIDS 2000;14(8):971-8. [PubMed]
  12. Tarwater PM, Gallant JE, Mellors JW, et al. Prognostic value of plasma HIV RNA among highly active antiretroviral therapy users. AIDS2004;18(18):2419-23. [PubMed]
  13. Gulick RM, Meibohm A, Havlir D, et al. Six-year follow-up of HIV-1-infected adults in a clinical trial of antiretroviral therapy with indinavir, zidovudine, and lamivudine. AIDS 2003;17(16):2345-9. [PubMed]
  14. Wu H, Mellors J, Ruan P, et al. Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors. J Acquir Immune Defic Syndr 2003;33(5):557-63. [PubMed]
  15. Porter DP, Kulkarni R, Fralich T, et al. 96-week resistance analyses of the STaR study: rilpivirine/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive, HIV-1-infected subjects. HIV Clin Trials 2015;16(1):30-8. [PubMed]
  16. Behrens G, Rijnders B, Nelson M, et al. Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA ≤100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis. AIDS Patient Care STDS 2014;28(4):168-75. [PubMed]
  17. Molina JM, Clumeck N, Redant K, et al. Rilpivirine vs. efavirenz in HIV-1 patients with baseline viral load 100,000 copies/ml or less: week 48 phase III analysis. AIDS 2013;27(6):889-97. [PubMed]
  18. Haubrich RH, Riddler SA, Ribaudo H, et al. Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection. AIDS 2011;25:2269-2278. [PubMed]
  19. Townsend D, Troya J, Maida I, et al. First HAART in HIV-infected patients with high viral load: Value of HIV RNA levels at 12 weeks to predict virologic outcome. J Int Assoc Physicians AIDS Care (Chic) 2009;8:314-317. [PubMed]
  20. Baxter JD, Mayers DL, Wentworth DN, et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS2000;14(9):F83-93. [PubMed]
  21. Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005;293:817-829. [PubMed]
  22. Lee PK, Kieffer TL, Siliciano RF, et al. HIV-1 viral load blips are of limited clinical significance. J Antimicrob Chemother 2006;57:803-805. [PubMed]
  23. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. January 28, 2016. www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
  24. Lopez Bernaldo de Quiros JC, Miro JM, Peña JM, et al. A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98. N Engl J Med 2001;344(3):159-67. [PubMed]
  25. El-Sadr WM, Burman WJ, Grant LB, et al. Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med 2000;342(15):1085-92. [PubMed]
  26. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 2007;44:441-446. [PubMed]
  27. Oldfield EC 3rd, Fessel WJ, Dunne MW, et al. Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial. Clin Infect Dis 1998;26(3):611-9. [PubMed]
  28. Havlir DV, Dubé MP, Sattler FR, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. California Collaborative Treatment Group. N Engl J Med 1996;335(6):392-8. [PubMed]
  29. Schneider MM, Hoepelman AI, Eeftinck Schattenkerk JK, et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group. N Engl J Med 1992;327(26):1836-41. [PubMed]
  30. Fischl MA, Dickinson GM, La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988;259(8):1185-9. [PubMed]
  31. Gras L, Kesselring AM, Griffin JT, et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. J Acquir Immune Defic Syndr 2007;45:183-192. [PubMed]
  32. Sabin CA, Smith CJ, d’Arminio Monforte A, et al., Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group. Response to combination antiretroviral therapy: Variation by age. AIDS 2008;22:1463-1473. [PubMed]
  33. Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009;48:787-794. [PubMed]
  34. Garcia F, de Lazzari E, Plana M, et al. Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count. J Acquir Immune Defic Syndr 2004;36:702-713. [PubMed]

HIV Resistance Assays

Medical Care Criteria Committee, June 2016

RECOMMENDATIONS
  • Clinicians should consult with an expert to interpret the results of resistance assays because such results are often complex (AIII). The NYSDOH AIDS Institute’s Clinical Education Initiative line is available for phone consultation: 800-637-2342.
  • When determining the optimal regimen for achieving viral suppression, clinicians should:
    • Perform genotypic resistance testing that includes the protease and reverse transcriptase genes:
      • At baseline, regardless of whether ART is being initiated (AII)
      • In ART-naïve patients before initiation of ART [a] (AII)
      • In patients experiencing treatment failure [b] or incomplete viral suppression; such testing should be performed while patients are still on therapy, but no longer than 4 weeks after stopping ART, given the rapid return of wild-type virus (AII)
    • Perform co-receptor tropism testing prior to initiation of a CCR5 antagonist (AI)
    • In cases where integrase or fusion inhibitor resistance is suspected, obtain these tests as a supplement to protease and reverse transcriptase testing (AII)

Notes:

  1. In the settings of pregnancy and acute infection, treatment should not be withheld while awaiting the results of resistance testing; adjustments may be made to the regimen once resistance results are available (see Diagnosis and Management of Acute HIV Infection.
  2. Virologic failure is defined as >200 copies/mL (see Virologic and Immunologic Monitoring).

The interpretation of HIV resistance assays is one of the most challenging tasks clinicians encounter when caring for HIV-infected patients and is crucial for tailoring an effective therapeutic ART regimen. The replicative mechanisms of HIV lack proof-reading capacity, making them error-prone and subject to cumulative mutations (i.e., changes in its genetic sequence). This lack of replicative fidelity, coupled with the selective pressure of sub-therapeutic drug levels, can lead to the development of clinically significant (i.e., resistance-bearing) mutations.

KEY POINT
  • Resistance testing is recommended when patients are interrupting incompletely suppressive ART. Because of the rapid return of wild-type virus without selective pressure from ART [1], testing is preferred before cessation of treatment. In cases where the patient has already stopped therapy, testing should be performed as soon as practical and no more than 4 weeks after cessation, before the return of wild-type virus. Mutations detected in this setting may provide useful information, but the absence of mutations does not rule out their presence in minor variants.

The most commonly used ART drugs are targeted to inhibit the activity of three specific viral enzymes: the protease, reverse transcriptase (RT), and integrase. Mutations have been identified that interfere with the ability of one or more ART agents to inhibit viral protein activity, thus rendering the virus resistant to the drug(s). HIV resistance mutations and mechanisms for less commonly used ART drugs that target fusion and viral entry have also been identified.

New resistance mutations and the emerging clinical significance of these mutations frequently change. Several resources are available for more information on drug resistance mutations and resistance testing, including:

Two methods are used to determine drug resistance for HIV: genotyping, which detects treatment-resistant genetic mutations; and phenotyping, which assesses the viral response to ART agents. Genotyping is the preferred test in most clinical situations.

In New York State, third-party reimbursement programs, including Medicaid, the New York State AIDS Drug Assistance Program (ADAP), and private insurers, often limit the number of resistance tests per year (within 12 months following date of first use). Medicaid Managed Care Plans (MMCPs) and private insurers may require prior authorization for these services and may limit the number of resistance tests performed annually, such as three tests per year, regardless of whether genotyping, phenotyping, or a combination of testing is obtained.

Providers should refer to their patient’s specific plan regarding frequency, annual limits, and whether prior authorization is required for any genotypic and phenotypic HIV resistance tests. Detailed information regarding Medicaid managed care-covered benefits for resistance testing, including current procedural terminology (CPT), codes is available at www.health.ny.gov/health_care/medicaid/program/update/2014/2014-03.htm#exp.

Investigational technologies, such as “single-copy” assays or “deep sequencing,” are under development; however, because they are not currently in use in clinical settings, these tests are not addressed here.

Genotyping

Genotypic resistance assays detect mutations known to be associated with therapeutic failure by directly sequencing the genomic coding region of the protein inhibited by the ART drug. The genomic mutations, which may include substitutions, insertions, or deletions in the viral protein’s coding region, are then compared with the known mutation(s) associated with the ART agent(s) clinical resistance profile.

Direct sequencing-based methods have been approved by the FDA, but the ViroSeq HIV-1 Genotyping System (Abbott Laboratories) is the only FDA-approved assay currently available. In addition, laboratory-developed (“in-house”) genotyping assays are available through several commercial laboratories (e.g., GenoSure MG, Monogram/LabCorp). Advances in genotyping assays continue to evolve. Testing for resistance to integrase strand transfer inhibitors and fusion inhibitors is now available and should be considered when resistance to these classes of drugs is a concern, such as when transmission of resistant virus is suspected or when a patient fails a regimen that includes one of these drugs.

In the RNA-based genotyping assays, the HIV-1 RNA is isolated from a plasma specimen and reverse-transcribed to produce complementary DNA (cDNA). Specific regions of the HIV genome are amplified by PCR and sequenced. This sequence is then compared with that of a drug-sensitive (“wild-type”) strain of HIV, and differences (mutations) present in the specimen sequence are noted. Computer software is generally used to perform this comparison and to predict whether resistance to specific drugs is likely to result from the particular combination of mutations detected in the virus. For most genotypic assays, this prediction is based on a set of rules derived from clinical observations, laboratory studies, and the advice of experts in the field. The actual prediction of resistance may vary from laboratory to laboratory for some combinations of mutations, depending on the interpretation algorithm used to define the rules.

Currently available RNA genotypic assays require a minimum viral load in the range of 500 to 2,000 copies/mL, depending on the assay, and generally require 2 weeks or less for results. DNA-based genotypic assays [2] are becoming commercially available, such as the GenoSure Archive (Monogram/LabCorp). These assays use next-generation sequencing technology and are designed to overcome the limitations that commonly used RNA genotypic assays encounter in the presence of low-level viremia. In traditional genotypic assays, identification of resistance mutations is often not possible when viral load levels are below the lower limit of detection of a given assay; the lower limit may range from 500 to 1,000 copies/mL across available assays.

In DNA-based genotypic assays, integrated proviral DNA is extracted from HIV-infected cells, rather than from the circulating HIV in the plasma. Once the proviral HIV cell-associated DNA is extracted, the DNA is PCR-amplified, sequenced, and analyzed in analogous fashion to the older genotype RNA methodologies. The coding sequences for reverse transcriptase-, protease-, and integrase-targeted inhibitors are matched, as with the RNA-resistance genotype assays, with known resistance-associated mutations. The results are usually reported as “sensitive,” “resistant,” or “resistance possible” for a given ART agent. Although the clinical efficacy of the DNA-based genotype assays has not been fully validated, this technology can provide information on “archived,” or noncirculating, viral resistance. It should not be assumed that all previous mutations will be detected. Although concordance across various studies using in-house, laboratory-developed tests was relatively high, the peripheral blood mononuclear cell (PBMC)-derived DNA assays often did not detect known previous mutations that had been documented with plasma-based RNA tests [3-5]; the results could vary by class, with the manufacturer’s own study showing lower concordance for protease mutations relative to those of reverse transcriptase in patients whose current viral load was undetectable [6]. However, testing of archived proviral DNA may provide useful additional information when making decisions about switching ART regimens for those who are virologically suppressed or those with repeated low-level viremia, especially when historical data are unavailable [7]. The commercial assay has not been validated for patients with viral loads >500 copies/mL, although some studies are investigating the assay’s performance at higher viral loads, when wild-type virus may have replaced drug-resistant variants typically detected by RNA-based assays [8]. The results obtained from archived proviral DNA testing should be used to supplement all other available information regarding treatment and resistance history.

Neither the RNA- nor DNA-based resistance assays can detect mutations associated with currently available HIV entry inhibitors (see below).

An older, algorithmic resistance profile based on genomic sequencing “virtual phenotype” (VIRCO, vircoTYPE) ceased to be clinically available in the United States as of December 2013. It compared the results of a patient’s genotype and predicted potential drug sensitivities by comparing a patient’s genotypic mutational profile with a database of laboratory and genotypic (sequence) and phenotypic (drug sensitivity) data and samples.

Phenotyping

Although still available, phenotypic assays generally do not add to the information provided by currently used genotypic assays. A phenotypic assay provides a direct measure of drug resistance and is analogous to antibiotic-susceptibility testing of bacteria. The currently available phenotypic assays use recombinant DNA methods to measure the ability of a patient’s virus to grow in the presence of a drug. Therefore, results from a phenotypic test include the net effect of any and all resistance mutations.

In the phenotypic assay, HIV RNA is isolated from plasma and converted into cDNA, and the relevant region is amplified by PCR. This amplified material is inserted into a recombinant virus system whereby the susceptibility to different drugs can be tested. The result from the phenotypic assay is a value that defines the concentration of the drug required to reduce growth of the virus by 50% (IC50). The IC50 of the patient’s virus is compared with the IC50 of a drug-sensitive (wild-type) reference virus, and the fold change is defined. If the IC50 of a person’s virus is greater than that of the reference virus for a particular drug, then the person’s virus has decreased sensitivity to the drug. The relative fold change helps determine whether the drug should still be included in the ART regimen or whether it should be removed entirely. Monogram Biosciences offers phenotypic resistance testing through clinical laboratories with the PhenoSense assay. Phenotypic assays have a minimum viral load requirement of 500 to 1,000 copies/mL and generally require 3 to 5 weeks for results. Phenotypic assays are more technically complex, labor-intensive, and expensive than genotypic assays.

Technical Limitations of Genotypic and Phenotypic Assays

In addition to the minimum viral load requirements needed for amplification (generally at least 500 to 1,000 copies/mL) in genotypic or phenotypic RNA-based resistance assays, all resistance assays, including the DNA-based genotype, are limited by sampling bias. Unlike acute infection, where infection is often established by a single progenitor virion [9] (see Diagnosis and Management of Acute HIV Infection), in established HIV infection, HIV exists as a virus population comprising multiple genomic variants. Genotypic and phenotypic resistance assays are each more likely to detect the common viral variants and fail to identify the minor variants. Similarly, standard genotypic and phenotypic resistance testing performed on plasma specimens will not detect noncirculating, or archived, resistant virus (i.e., virus resistant to ART agents from previous regimens). If therapy is stopped altogether, the selective pressure from the ART agents suppressing the noncirculating virus is removed and a pan-sensitive or wild-type HIV population over time will begin to resurface and dominate the circulating virus population. When this occurs, the RNA-based genotypic and phenotypic resistance assays may fail to detect the ART-resistant virus, despite being present either as archived virus or at low levels. Although a DNA-based assay may have utility in these circumstances, clinical data are insufficient to recommend for or against its use in the patient care setting. For these reasons, all copies of the patient’s previous genotype and/or phenotype resistance testing, along with the ART medication history, should be retained, and the information should be combined and used in constructing a subsequent ART regimen. Once resistance develops, it can be expected to persist indefinitely to that specific drug in archived form.

Another, more subtle, limitation is related to the level at which a virus is sensitive to a given ART agent. This “cutoff” may vary across assays, even when the same viral sample is used. Consultation with an experienced provider for interpretation of results is crucial.

Co-Receptor Tropism Assay

Co-receptor tropism analysis determines which cellular co-receptor (CCR5 or CXCR4) is used by the HIV-infected individual’s dominant viral population to gain access to host cells. The majority of acutely or recently infected individuals, including perinatally infected children, have a CCR5-tropic virus.

Because CCR5-tropic virus predominates early in HIV infection, whereas CXCR4-tropic virus is often present in late-stage disease, the CCR5 variant may be preferentially transmitted compared with CXCR4 variants. In chronically HIV-infected individuals, a population of mixed CCR5- and CXCR4-tropic viruses, as well as dual-tropic viruses, may also be detected. The tropism of these viral populations is often referred to as dual/mixed or D/M HIV.

In the United States, most co-receptor tropism testing involves phenotypic assays. However, genotypic assays, which predict tropism based on algorithmic analysis of viral V3 sequencing binding site [10, 11], are also available.

Although phenotypic testing can determine a viral population containing both tropisms, it is not sufficiently sensitive to differentiate between mixed and dual tropism. The Trofile (Monogram Biosciences) co-receptor tropism assay is an RNA-based test that permits phenotypic identification of CCR5, CXCR4 co-receptor, or dual/mixed-tropic (CXCR4/CCR5-utilizing) HIV-1 and should be used prior to the initiation of a receptor antagonist.

Another commercially available recombinant phenotypic assay for assessing HIV chemokine co-receptor tropism is the Phenoscript assay (Eurofins VIRalliance). In this assay, a 900-bp portion containing the patient’s V1-V3 envelope virus is amplified and inserted into a HIV-1 vector lacking the corresponding V1-V3 section. The fully complemented HIV-1 is then able to produce virus that can be used to infect cell lines with either CCR5 or CXCR4 on their surfaces with a colorimetric readout. The results are reported in a similar manner as the Trofile (i.e., CCR5-trophic, CXCR4-trophic, or dual/mixed tropic). This assay has not been validated in a clinical trial setting or against the Trofile assay.

Two DNA-based tropism assays are also available. The HIV-1 Coreceptor Tropism, Proviral DNA (Quest Diagnostics) uses population sequencing of the HIV envelope V3 loop to detect the presence of CXCR4-tropic HIV-1 [12]. The Trofile DNA (Monogram Biosciences) uses the complete gp160 coding region to distinguish whether the HIV-1 population uses CCR5, CXCR4, or both (i.e., dual/mixed tropism) to gain entry into the cell. Unlike HIV-1 RNA-based assays, both the Trofile DNA and HIV-1 Coreceptor Tropism can detect virus in the setting of undetectable HIV-1 viral load levels and should be used when HIV RNA is beneath the lower limit recommended for RNA-based tropism assays (<1,000 copies/mL).

Resistance to the class of CCR5 co-receptor antagonists develops by two unrelated mechanisms. First, the patient’s viral population shifts its co-receptor usage (i.e., uses CXCR4 exclusively or uses both CCR5 and CXCR4 receptors to gain entry into the cell). The current assays are not sufficiently sensitive to discriminate between mixed- or dual-tropic populations. The second method by which resistance to a CCR5 receptor antagonist may develop is by the virus mutating and binding to the CCR5 receptor with the drug antagonist still in place. This second method can be discerned by a flattening of the IC90curves in a phenotypic assay or potentially by genotypic analysis. Analysis by phenotypic assay is the preferred method for this purpose because genotypic data are more complex.

Replicative Capacity

Replicative capacity information may be provided as an adjunct to phenotypic or combination genotypic-phenotypic resistance assays. The relative replicative capacity of the virus from the patient is calculated as the ratio of the patient-derived sequences to wild-type sequences. A ratio of less than 1 reflects a reduced replicative capacity as compared with that of the wild-type control. The full clinical value of this adjunctive information remains under investigation, and it has no clear clinical value at this time.

References:
  1. Devereux HL, Youle M, Johnson MA, et al. Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy. AIDS1999;13:F123-F127. [PubMed]
  2. White KL, Toma J, Napolitano LA et al. Genotypic analyses of pre-existing HV-1 drug resistance in proviral HIV-1DNA from PBMCs in suppressed patients switching to RPV/FTC/TDF. International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies. June 4-8, 2013 Toronto, Canada. Abstract 57.
  3. Banks L, Gholamin S, White E, et al. Comparing peripheral blood mononuclear cell DNA and circulating plasma viral RNA pol genotypes of subtype C HIV-1. J AIDS Clin Res 2012;3:141-147. [PubMed]
  4. Delaugerre C, Braun J, Charreau I, et al. Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed replication. HIV Med 2012;13:517-525. [PubMed]
  5. Lübke N, Di Cristanziano V, Sierra S, et al. Proviral DNA as a target for HIV-1 resistance analysis. Intervirology 2015;58:184-189. [PubMed]
  6. Toma J, Tan Y, Cai S, et al. Drug resistance profiles derived from HIV-1 DNA in ARV suppressed patients correlate with historical resistance profiles obtained from HIV-1 plasma RNA. ICAAC 2015, September 17-21, 2015, San Diego. http://www.natap.org/2015/ICAAC/ICAAC_10.htm
  7. Booth CL, McCormick A, Garcia-Diaz A, et al. Feasibility of testing and detection of HIV-1 drug resistance in pro-viral DNA. BMC Infect Dis 2014;14(Suppl 4)14:O25. http://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-14-S4-O25
  8. Derache A, Shin HS, Balamane M, et al. HIV drug resistance mutations in proviral DNA from a community treatment program. PLoS One2015;10:e0117430. [PubMed]
  9. Cohen MS, Shaw GM, McMichael AJ, et al. Acute HIV-1 infection. N Engl J Med 2011;364:1943-1954. [PubMed]
  10. Vandekerckhove L, Verhofstede C, Vandenbroucke I, et al. Direct comparison with 454 pyrosequencing validates V3-loop based genotyping in patients eligible for Maraviroc initiation. ICAAC, September 15, 2009, San Francisco, CA. Abstract.
  11. McGovern RA, Thielen A, Mo T, et al. Population-based V3 genotypic tropism assay: A retrospective analysis using screening samples from the A4001029 and MOTIVATE studies. AIDS 2010;24:2517-2525. [PubMed]
  12. Baumann R, Hamdan H, Schwab D. Performance of an HIV-1 co-receptor tropism assay utilizing replicate V3 loop sequencing and heteroduplex analysis with capillary electrophoresis. Presented at the 18th International HIV Drug Resistance Workshop, June 9-12, 2009, Ft. Myers, FL. Antivir Ther 2009;14:A132. Abstract.

Laboratory Monitoring of ART Side Effects

Medical Care Criteria Committee, March 2006 (unless noted otherwise noted)

This section describes monitoring of the following ART side effects: bone marrow suppression, pancreatitis, lactic acidosis/hepatic steatosis, hepatotoxicity, and renal toxicity. (See Table 14: Antiretroviral Therapy-Associated Common and/or Severe Adverse Effects, in the DHHS guidelines for a table of common and/or severe adverse effects associated with ART).

Bone Marrow Suppression

RECOMMENDATION
  • Complete blood counts should be measured before initiation of ART therapy and at least every 4 months thereafter. For patients at high risk for bone marrow toxicity (e.g., those with advanced HIV infection, those with pre-treatment cytopenias, or those who are receiving zidovudine), blood counts may have to be monitored more frequently because significant cytopenias may occur. (III)

Bone marrow suppression is most often associated with zidovudine therapy. Significant drug-induced cytopenias become more common in the later stages of symptomatic HIV infection but occasionally develop abruptly in patients at earlier stages.

Pancreatitis

RECOMMENDATIONS
  • When patients receiving ART present with signs or symptoms suggestive of pancreatitis, clinicians should obtain serum amylase and lipase levels. (III)
  • If signs or symptoms of pancreatitis occur in patients taking antiretroviral medications, the clinician should temporarily suspend the entire ART regimen. A new ART regimen may be initiated when enzymes are normalized but should not include antiretroviral medications that are most likely linked to pancreatitis, such as didanosine or stavudine.
  • An elevated serum amylase level should be confirmed with a serum lipase level. (III)
  • Clinicians should not prescribe didanosine for patients who have a history of pancreatitis. (III)

The incidence of pancreatitis is higher in patients infected with HIV and may be associated with opportunistic infections as well as ART. Didanosine has been the agent most often associated with this complication; however, cases of pancreatitis also have been reported with other antiretroviral agents since the advent of triple combination therapy. Tenofovir increases the levels of didanosine, thereby increasing the theoretical risk of pancreatitis. Thus, when these antiretroviral medications are used in combination, the dose of didanosine should be reduced.

Pancreatitis should be considered in any patient receiving ART who presents with signs or symptoms of pancreatitis (e.g., abdominal pain, persistent nausea, and vomiting), and serum amylase and lipase should be obtained in this setting. Significant hypertriglyceridemia (>500 mg/dL) is associated with an increased risk of pancreatitis, particularly in patients with other risk factors for pancreatitis (e.g., alcohol or didanosine use). Other causes linked to pancreatitis in the general population should be included in the differential diagnosis.

Hyperamylasemia of non-pancreatic (e.g., parotid) origin may occur in HIV-infected patients. Serum lipase levels should be obtained to delineate the source of the increased amylase. Asymptomatic patients with modest elevations in amylase and lipase levels (<3-fold) may be monitored closely without change in therapy.

Lactic Acidosis/Hepatic Steatosis

RECOMMENDATIONS
  • When patients develop symptoms consistent with lactic acidosis syndrome in conjunction with an elevated lactate level (>2 mmol/L) and decreased serum bicarbonate (<20 mmol/L), the clinician should temporarily discontinue the entire ART regimen while an evaluation is conducted. (II)
  • Routine monitoring of serum lactate levels is not indicated in asymptomatic patients. (I)
  • Patients who are asymptomatic and have an unexplained decrease in serum bicarbonate level (<20 mmol/L) should be promptly re-evaluated with a repeat test and a venous or arterial lactate. (II) If a venous lactate is mildly elevated (2.1 to 5.0 mmol/L), an arterial lactate should be obtained, and re-assessment for the presence of symptoms associated with lactic acidosis should be performed. (I) If the lactate is persistently elevated, the arterial pH is abnormal, or the patient has become symptomatic, ART should be discontinued. (III)

The syndrome of lactic acidosis/hepatic steatosis is rare but associated with a high mortality rate and has been most often associated with the use of NRTIs. Groups at higher risk for this complication include African Americans, obese patients, female patients, and patients with chronic hepatitis C virus (HCV). The syndrome is marked by constitutional complaints, such as abdominal pain, anorexia, nausea/vomiting, hyperventilation, and/or myalgias associated with elevations in serum lactate levels and decreased serum bicarbonate levels. Blood sampling for venous lactate levels should avoid the use of prolonged tourniquetting, and samples should be transported on ice and processed promptly. Lactic acidosis is believed to manifest only at lactate levels >5 mmol/L with an accompanying decreased bicarbonate level.

Patients taking NRTIs who present with constitutional symptoms should be evaluated for lactic acidosis, including lactate (arterial or venous) and bicarbonate level, arterial blood gas determination, serum amylase and lipase, and serum liver enzymes. In conjunction with the evaluation, ART should be discontinued. If the evaluation does not support the diagnosis of lactic acidosis, ART may be restarted.

Patients with mildly elevated lactate levels (2.1 to 5.0 mmol/L) and a normal bicarbonate level are usually asymptomatic. The clinical significance of mildly elevated lactate levels is still unknown. In the absence of decreased bicarbonate levels, lactic acidosis is uncommon.

Hepatotoxicity

January 2007

RECOMMENDATIONS
  • Clinicians should obtain serum liver enzyme levels at baseline and every 3 to 4 months thereafter in patients receiving ART. (III)
  • Clinicians should screen for alcohol use in patients with abnormal serum liver enzyme levels. (III)

Use of Nevirapine

  • Clinicians should not use nevirapine as part of the initial regimen in women with CD4 counts >250 cells/mm3 or men with CD4 counts >400 cells/mm3 because of an increased incidence of hepatotoxicity. (I)
  • When initiating an ART regimen that includes nevirapine, clinicians should obtain serum liver enzymes at baseline, at the time of dose escalation (14 days), and 2 weeks after dose escalation. (III)
  • Clinicians should counsel patients to seek medical evaluation when signs and symptoms of hepatitis, severe skin reactions, or hypersensitivity reactions related to nevirapine occur. Serum liver enzymes should be obtained whenever patients develop a rash during nevirapine therapy, particularly during the first 18 weeks of therapy. (II)
  • In the setting of hepatotoxicity related to nevirapine, patients should not be re-challenged with nevirapine. (I)

All antiretroviral agents have the potential to cause abnormalities in liver function, especially in patients with preexisting liver disease. Serum liver enzyme levels should be obtained at baseline and every 3 to 4 months in patients receiving ART. More frequent monitoring may be necessary for patients with preexisting liver disease or serum liver enzyme abnormalities. The use of full-dose ritonavir (600 mg twice daily) has been associated with worsening transaminases in patients with preexisting liver disease and should be avoided. Patients who develop serum liver enzyme abnormalities greater than five times the upper limit of normal should be promptly assessed. Any potentially hepatotoxic medication, including all antiretroviral agents, should be discontinued.

A higher incidence of significant hepatotoxicity associated with nevirapine therapy has recently been reported, especially in women with CD4 counts >250 cells/mm3, men with CD4 counts >400 cells/mm3, and in the setting of HCV coinfection. The greatest risk of severe and potentially fatal hepatotoxicity occurs in the first 6 weeks of treatment; however, the FDA and the manufacturer strongly recommend intensive monitoring during the first 18 weeks of nevirapine therapy, with discontinuation of the drug if moderate or severe abnormalities occur. In the absence of definitive clinical evidence, monitoring serum liver enzymes every 2 weeks for the first month of nevirapine therapy, then monthly for the first 12 weeks, and every 1 to 3 months thereafter is a reasonable approach, given the potential severity of adverse events. It is essential that the 14-day lead-in period be strictly followed. In some cases, the hepatic injury progresses even after discontinuation of nevirapine. In the setting of hepatotoxicity related to nevirapine, the patient should not be re-challenged with nevirapine.

Some clinicians would avoid using efavirenz after severe nevirapine-related hepatotoxicity (LFTs >5x ULN) with or without Grade 4 rash (Stevens-Johnson syndrome); however, there is no clear evidence to support an association between nevirapine-related hepatotoxicity and efavirenz-related hepatotoxicity [1]. For mild to moderate nevirapine-related hepatotoxicity (LFTs >3-5 x ULN), switching to efavirenz after complete resolution of hepatotoxicity is an option if there are no other contraindications to efavirenz. Contraindications to efavirenz include known adverse reactions to efavirenz, first-trimester pregnancy, or strong likelihood of becoming pregnant.

For pregnant women with nevirapine-related hepatotoxicity, the clinician should switch the regimen to 2 NRTIs + PI. Efavirenz should only be considered after the first 8 weeks of pregnancy if there are no other options and the benefits outweigh the risks. For additional information, see the DHHS Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.

In the setting of severe nevirapine-related hepatotoxicity, all antiretroviral agents and any other possible offending agents should be discontinued. The risk of severe hepatotoxicity outweighs the risk of possible emergence of resistance. 

Renal Toxicity

September 2012

RECOMMENDATIONS
For all HIV-infected patients receiving ART:
  • Clinicians should routinely assess kidney function in all HIV-infected patients. A renal assessment should include:
    • Glomerular filtration rate estimated from serum creatinine (baseline and at least every 6 months) (AII)
    • Blood urea nitrogen (baseline and at least every 6 months) (AIII)
    • Urinalysis (baseline and at least annually) (AIII)
    • For patients with diabetes and no known proteinuria: calculation of urine albumin-to-creatinine ratio to detect microalbuminuria (baseline and at least annually) (AI)
For patients receiving tenofovir:
  • For patients initiating a tenofovir-containing regimen, clinicians should calculate glomerular filtration rates at initiation of therapy, 1 month after initiation of therapy, and then at least every 4 months thereafter.
  • Clinicians should adjust tenofovir dosing when glomerular filtration rate approaches 50 mL/min or discontinue tenofovir according to clinical status. (AII)
For patients receiving indinavir:
  • Clinicians should counsel patients receiving indinavir to drink at least 48 ounces of fluid per day.

HIV infection has been associated with several renal complications that may lead to renal insufficiency or failure [2, 3]. Renal impairment necessitates dose adjustment or discontinuation of many antiretroviral agents.

Clinicians should routinely obtain urinalysis and serum creatinine levels as well as calculate glomerular filtration rates (GFR) to assess renal function. When calculating GFR, the clinician should consistently use the same method. GFR can be calculated by using one of the following equations:

Tenofovir is excreted by glomerular filtration and tubular secretion. Renal impairment has been reported in patients receiving tenofovir [3, 4]. The extent of this toxicity is unclear. Additional risk factors include low body weight, older age, use of boosted regimens, hypertension, diabetes, and use of other nephrotoxic drugs. Hypophosphatemia may be an early indicator of renal failure. Clinicians may want to use a lower threshold for dose adjustment in patients receiving tenofovir. Clinicians should discontinue tenofovir when patients present with symptoms suggestive of Fanconi syndrome, such as declining renal function with associated metabolic acidosis, hypophosphatemia, hypokalemia, glycosuria, and uricosuria. The decision to rechallenge with tenofovir should be made on a case-by-case basis.

Indinavir (especially when used with ritonavir) and agents used to prevent and/or treat opportunistic infections may cause hematuria, pyuria, or crystalluria. Patients receiving indinavir should be counseled to drink at least 48 ounces of fluid per day. Clinicians should consider urinalysis every 3 to 4 months for patients receiving indinavir-containing regimens.

For additional information regarding renal assessment and management of kidney disease in HIV-infected patients, see Kidney Disease in HIV-Infected Patients.

References:
  1. Sulkowski MS, Thomas DL, Mehta SH, et al. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections. Hepatology 2002;35;182-189. [PubMed] The greatest risk of NNRTI-associated severe hepatotoxicity was observed in patients taking NVP, those with hepatitis B or C co-infection, and those co-administered PIs.
  2. Miro JM, Cofan F, Trullas JC, et al. Renal dysfunction in the setting of HIV/AIDS. Curr HIV/AIDS Rep 2012;9:187-199. [PubMed] HIV-infected individuals commonly experience renal complications and have a high prevalence of risk factors, including HIV infection itself, that contribute to the development of kidney disease.
  3. Zaidan M, Lescure FX, Brochériou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: A clinico-pathological study. Clin J Am Soc Nephrol 2013;8:930-938. [PubMed] Drug toxicity, infection, and syndromes associated with immunosuppression in the setting of HIV demonstrate the importance of monitoring kidney function HIV-infected patients.
  4. Laprise C, Baril JG, Dufresne S, et al. Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: Results from 10 years of follow-up. Clin Infect Dis 2013;56:567-575. [PubMed] Tenofovir exposure significantly increased the risk of kidney dysfunction, but the loss in estimated glomerular filtration rate due to TDF was relatively mild over the long term.

Monitoring for ART-Associated Allergic Reactions

Medical Care Criteria Committee, June 2010

RECOMMENDATIONS
  • When patients receive any new antiretroviral drugs, clinicians should educate them about the possibility of ART-associated allergic reactions, including a hypersensitivity reaction, and the range of possible symptoms (see Table 4). (III)
  • Clinicians should discontinue offending drugs when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever. (I)
  • Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.
  • Clinicians should avoid re-challenging patients with a medication that has been associated with a hypersensitivity reaction, especially in the setting of abacavir reactions and severe NNRTI reactions. (I)
  • In patients who develop mild rash in response to nevirapine, clinicians should avoid escalating the nevirapine dose to twice daily until after the rash has resolved. For patients with moderate to severe cutaneous toxicity, nevirapine should be discontinued and should not be re-challenged. Use of an alternate NNRTI should be avoided. (III)
Table 4: Antiretroviral Drugs Typically Associated with Allergic Reactions
ARV Drug (usual timing of symptoms) Most Frequent Symptoms  Action
Abacavir* (first 4-6 weeks after initiation) Hypersensitivity reaction: Fever, headache, gastrointestinal symptoms, malaise, arthralgias, myalgias, and respiratory problems. Skin involvement, with rash and pruritus may be mild or absent.
  • Prompt discontinuation of abacavir
  • Do not re-challenge
Delavirdine (first 4 weeks after initiation)  Mild to moderate cutaneous allergy
  • Consider systemic antihistamines while continuing delavirdine for mild rashes
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Efavirenz (first 4 weeks after initiation)  Mild to moderate cutaneous allergy
  • Consider systemic antihistamines while continuing efavirenz for mild rashes
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Enfuvirtide In the phase 3 trials of enfuvirtide, three cases of probable hypersensitivity were identified. These included, either individually or in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated LFTs.  —
Etravirine (generally occurs in the 2nd week of treatment; infrequent after week 4)

Severe reaction: Cutaneous, involving the mucocutaneous surfaces (Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme)

Mild reaction: mild skin rash

 Severe reaction:

  • Discontinue etravirine promptly
  • Discontinue if rash accompanied by fever, hepatitis, and other systemic symptoms.
  • Obtain serum liver enzyme levels
  • Grade 3 and 4 rashes reported in 1.3% of patients
  • Rash more common in women

Mild reaction: Manage with antihistamines and close monitoring

Fosamprenavir, tipranavir, and darunavir  Mild to moderate cutaneous allergy
  • Patients with sulfa allergy may be at increased risk of developing an allergic reaction
  • For mild rashes, consider using systemic antihistamines while continuing protease inhibitors with sulfa moiety
  • Discontinue when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever
Nevirapine (first 2 to 18 weeks after initiation)

Severe reaction: Cutaneous, involving the mucocutaneous surfaces (Stevens-Johnson syndrome), often accompanied by fever and severe hepatitis

Mild reaction: mild skin rash

 Severe reaction:

  • Discontinue nevirapine promptly
  • Obtain serum liver enzyme levels
  • Do not re-challenge
  • Do not use alternate NNRTI (however, patients with NNRTI rash did not have a higher incidence of rash when given etravirine)

Mild reaction:

  • Close monitoring recommended, but most clinicians would switch to an alternative antiretroviral
  • Obtain serum liver enzyme levels
  • Do not escalate dose to twice daily until the rash has resolved
Raltegravir Rashes, including severe skin rashes and cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported Discontinue if rash is accompanied by constitutional symptoms (i.e., fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema)
*HLA-B*5701 is a pharmacogenetic test (HLA-B*5701) used to identify patients who are predisposed to abacavir hypersensitivity. Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.

Many medications pose the risk of causing various types of allergic reactions, typically presenting as maculopapular rash, with or without fever. Occasionally, a more severe hypersensitivity reaction occurs, consisting of rash and fever, with a combination of other symptoms, such as headache, arthralgias, hepatitis, eosinophilia, and GI or respiratory symptoms. The hypersensitivity reaction usually occurs within 2 to 6 weeks after the drug is started.

Although trimethoprim/sulfamethoxazole is the drug most frequently implicated in common allergic reactions in HIV-infected patients, abacavir, darunavir, tipranavir, fosamprenavir, all of the NNRTIs (nevirapine, delavirdine, efavirenz, etravirine), and enfuvirtide (less commonly) have been associated with a hypersensitivity reaction or syndrome (see Table 4). These reactions are for the most part idiosyncratic and unanticipated. The reactions to darunavir, fosamprenavir, tipranavir (all have a sulfa moiety), delavirdine, and efavirenz are generally mild to moderate cutaneous allergy (drug rash). Patients may rarely develop severe mucous membrane involvement with systemic toxicity. Occasionally, patients will only have a fever. Clinicians should discuss the possibility of these reactions with patients initiating ART because they are most commonly seen in the first 4 weeks of treatment; clinicians should educate patients about the symptoms of hypersensitivity.

Systemic antihistamines may be useful in treating mild cases while patients continue to receive the offending drug. The offending drug should be discontinued when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever.

Individuals with human leukocyte Ag (HLA)-B*5701, HLA-DR7, and HLA-DQ3 have a genetic predisposition to development of abacavir hypersensitivity. HLA-B*5701 testing is the most thoroughly documented method for assessing for abacavir hypersensitivity and should be determined prior to treatment with this agent [1, 2]. Unlike virus-specific tests (HIV genotype, phenotype, co-receptor tropism assays), HLA genotyping is necessary only once during an individual’s lifetime, because it will not change over time.

Hypersensitivity to abacavir occurred in as many as 5% of patients before routine HLA-B*5701 testing was recommended. The reaction usually occurs within the first 10 to 14 days of therapy and rarely occurs after the first 6 weeks. Fever, headache, GI symptoms, malaise, arthralgias, myalgias, and respiratory problems are the most frequent manifestations of the abacavir hypersensitivity reaction. Skin involvement, with rash and pruritus, may be mild or absent. HLA-B*5701 is a pharmacogenetic test (HLA-B*5701) used to identify patients who are predisposed to abacavir hypersensitivity. Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.

Prompt discontinuation of abacavir when a hypersensitivity reaction is suspected is necessary because symptoms will worsen over time. Once abacavir has been discontinued because of a possible or definite hypersensitivity reaction, abacavir should never be administered again. Re-challenge may result in an anaphylactic reaction with associated hypotension or death.

Nevirapine, an NNRTI, has been associated with severe hypersensitivity reactions in the first 2 to 12 weeks of use. Graduated dosing of nevirapine at initiation with 200 mg daily for the first 2 weeks followed by 200 mg twice daily thereafter has reduced the incidence of hypersensitivity reactions. Systemic antihistamines or corticosteroids given at the time of nevirapine initiation have not been proven useful. Such reactions manifest as severe cutaneous reaction involving the mucocutaneous surfaces (Stevens-Johnson syndrome), often with accompanying fever and severe hepatitis. Deaths associated with these reactions have been reported. Patients who develop mild rashes without systemic toxicity may be managed with antihistamines and close monitoring. The nevirapine dose should not be escalated to twice daily until the rash has resolved. However, those with moderate to severe cutaneous toxicity should discontinue nevirapine promptly and should not be re-challenged with this drug. Because of potential cross-reactivity, use of an alternate NNRTI should be avoided in patients who have a severe reaction to nevirapine; however, the incidence of etravirine rash is not high in patients with a history of NNRTI rash.

Etravirine, an NNRTI, has been associated with hypersensitivity reaction. Up to 10% of patients in clinical trials reported rashes. Most reported mild to moderate rashes. Grade 3 and 4 rashes reported in 1.3% of patients, and up to 2.2% of patients required etravirine discontinuation. Rashes generally occur in the second week of treatment and are infrequent after week 4. Etravirine should be discontinued for severe rash or if rash is accompanied by fever, hepatitis, and other systemic symptoms.

In the phase 3 trials of enfuvirtide, three cases of probable hypersensitivity to the drug were identified. These have included, either individually or in combination, rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum liver enzymes.

References:
  1. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir. Lancet 2002;359:727-732. [PubMed]
  2. Hetherington S, Hughes AR, Mosteller M, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet2002;359:1121-1122. [PubMed]

All Recommendations

Medical Care Criteria Committee

ALL RECOMMENDATIONS: MONITORING OF PATIENTS ON ART
Virologic and Immunologic Monitoring (June 2016)
  • Clinicians should monitor HIV RNA levels and CD4 counts according to the recommended intervals in Table 1. Follow-up visits should be scheduled more frequently as clinically necessary to address non-HIV-related conditions, secondary prevention, and issues that may affect adherence to ART or retention in care, such as substance use, mental health disorders, unstable housing, or need for supportive services. (AIII)
  • Clinicians should perform resistance testing under the following circumstances:
    • At baseline, regardless of whether ART is being initiated (genotypic testing)
    • In ART-naïve patients before initiation of ART (genotypic testing) (III)
    • In patients experiencing treatment failure or incomplete viral suppression while receiving ART (genotypic and/or phenotypic testing) (I)
  • When resistance testing is indicated, it optimally should be performed while patients are either receiving therapy or have been off therapy for less than 1 year. (III)
HIV Resistance Assays (June 2016)
  • Clinicians should consult with an expert to interpret the results of resistance assays because such results are often complex (AIII) (the NYSDOH AIDS Institute’s Clinical Education Initiative line is available for phone consultation: 800-637-2342)
  • When determining the optimal regimen for achieving viral suppression, clinicians should:
    • Perform genotypic resistance testing that includes the protease and reverse transcriptase genes:
      • At baseline, regardless of whether ART is being initiated (AII)
      • In ART-naïve patients before initiation of ART [a] (AII)
      • In patients experiencing treatment failure [b] or incomplete viral suppression; such testing should be performed while patients are still on therapy, but no longer than 4 weeks after stopping ART, given the rapid return of wild-type virus (AII)
    • Perform co-receptor tropism testing prior to initiation of a CCR5 antagonist (AI)
    • In cases where integrase or fusion inhibitor resistance is suspected, obtain these tests as a supplement to protease and reverse transcriptase testing (AII)
Laboratory Monitoring of HIV Side Effects
  • Bone marrow suppression (March 2006)
    • Complete blood counts should be measured before initiation of ART therapy and at least every 4 months thereafter. For patients at high risk for bone marrow toxicity (e.g., those with advanced HIV infection, those with pre-treatment cytopenias, or those who are receiving zidovudine), blood counts may have to be monitored more frequently because significant cytopenias may occur. (III)
  • Pancreatitis (March 2006) 
    • When patients receiving ART present with signs or symptoms suggestive of pancreatitis, clinicians should obtain serum amylase and lipase levels. (III)
    • If signs or symptoms of pancreatitis occur in patients taking antiretroviral medications, the clinician should temporarily suspend the entire ART regimen. A new ART regimen may be initiated when enzymes are normalized but should not include antiretroviral medications that are most likely linked to pancreatitis, such as didanosine or stavudine.
    • An elevated serum amylase level should be confirmed with a serum lipase level. (III)
    • Clinicians should not prescribe didanosine for patients who have a history of pancreatitis. (III)
  • Lactic acidosis/hepatic steatosis (March 2006)
    • When patients develop symptoms consistent with lactic acidosis syndrome in conjunction with an elevated lactate level (>2 mmol/L) and decreased serum bicarbonate (<20 mmol/L), the clinician should temporarily discontinue the entire ART regimen while an evaluation is conducted. (II)
    • Routine monitoring of serum lactate levels is not indicated in asymptomatic patients. (I)
    • Patients who are asymptomatic and have an unexplained decrease in serum bicarbonate level (<20 mmol/L) should be promptly re-evaluated with a repeat test and a venous or arterial lactate. (II) If a venous lactate is mildly elevated (2.1 to 5.0 mmol/L), an arterial lactate should be obtained, and re-assessment for the presence of symptoms associated with lactic acidosis should be performed. (I) If the lactate is persistently elevated, the arterial pH is abnormal, or the patient has become symptomatic, ART should be discontinued. (III)
  • Hepatotoxicity (January 2007)
    • Clinicians should obtain serum liver enzyme levels at baseline and every 3 to 4 months thereafter in patients receiving ART. (III)
    • Clinicians should screen for alcohol use in patients with abnormal serum liver enzyme levels. (III)
    • Use of nevirapine:
      • Clinicians should not use nevirapine as part of the initial regimen in women with CD4 counts >250 cells/mm3 or men with CD4 counts >400 cells/mm3 because of an increased incidence of hepatotoxicity. (I)
      • When initiating an ART regimen that includes nevirapine, clinicians should obtain serum liver enzymes at baseline, at the time of dose escalation (14 days), and 2 weeks after dose escalation. (III)
      • Clinicians should counsel patients to seek medical evaluation when signs and symptoms of hepatitis, severe skin reactions, or hypersensitivity reactions related to nevirapine occur. Serum liver enzymes should be obtained whenever patients develop a rash during nevirapine therapy, particularly during the first 18 weeks of therapy. (II)
      • In the setting of hepatotoxicity related to nevirapine, patients should not be re-challenged with nevirapine. (I)
  • Renal toxicity (September 2012)
    • For all HIV-infected patients receiving ART, clinicians should routinely assess kidney function with an assessment that includes:
      • Glomerular filtration rate estimated from serum creatinine (baseline and at least every 6 months) (AII)
      • Blood urea nitrogen (baseline and at least every 6 months) (AIII)
      • Urinalysis (baseline and at least annually) (AIII)
      • For patients with diabetes and no known proteinuria: calculation of urine albumin-to-creatinine ratio to detect microalbuminuria (baseline and at least annually) (AI)
  • For patients initiating a tenofovir-containing regimen, clinicians should calculate glomerular filtration rates at initiation of therapy, 1 month after initiation of therapy, and then at least every 4 months thereafter.
    • Clinicians should adjust tenofovir dosing when glomerular filtration rate approaches 50 mL/min or discontinue tenofovir according to clinical status. (AII)
  • Clinicians should counsel patients receiving indinavir to drink at least 48 ounces of fluid per day.
Monitoring for ART-Associated Allergic Reactions (June 2010)
  • When patients receive any new antiretroviral drugs, clinicians should educate them about the possibility of ART-associated allergic reactions, including a hypersensitivity reaction, and the range of possible symptoms (see Table 4). (III)
  • Clinicians should discontinue offending drugs when there is a moderate to severe skin reaction, mucous membrane involvement, systemic toxicity, or fever. (I)
  • Clinicians should perform HLA-B*5701 testing before initiating abacavir-based therapy.
  • Clinicians should avoid re-challenging patients with a medication that has been associated with a hypersensitivity reaction, especially in the setting of abacavir reactions and severe NNRTI reactions. (I)
  • In patients who develop mild rash in response to nevirapine, clinicians should avoid escalating the nevirapine dose to twice daily until after the rash has resolved. For patients with moderate to severe cutaneous toxicity, nevirapine should be discontinued and should not be re-challenged. Use of an alternate NNRTI should be avoided. (III)
Notes
  1. In the settings of pregnancy and acute infection, treatment should not be withheld while awaiting the results of resistance testing; adjustments may be made to the regimen once resistance results are available (see Diagnosis and Management of Acute HIV Infection.
  2. Virologic failure is defined as >200 copies/mL (see Virologic and Immunologic Monitoring).

Primary Care Approach Guideline

Introduction

Medical Care Criteria Committee, April 2011

RECOMMENDATIONS
  • Primary care clinicians should be capable of evaluating HIV-infected patients at all stages of HIV infection and should consult with a clinician who has experience with management of antiretroviral therapy (ART) according to current guidelines (see Antiretroviral Therapy). (III)
  • Clinicians should involve patients in decisions regarding HIV treatment. (III)

As the treatment of HIV has continued to reduce mortality and increase the number of clinically stable patients, the primary care approach to HIV-infected patients has evolved. In addition to the management of HIV infection, a renewed emphasis on general preventive medicine has emerged. The following aspects of care are discussed:

  • Medical history and physical examination
  • Laboratory assessments and diagnostic testing
  • Health maintenance and preventive care
  • Coordination of care
  • Use of chronic care services

For treatment considerations, see Antiretroviral Therapy.

History and Ongoing Assessments

November 2014

RECOMMENDATIONS
  • Clinicians should obtain a baseline and an ongoing HIV-related history according to Table 1. (AI)
  • When obtaining an HIV-related history, clinicians should:
    • Use vocabulary that patients can understand, regardless of educational level (AIII)
    • Assess patients’ health literacy* (AIII)
    • Determine the language in which the patient wishes to communicate and use a professional interpreter or sign language services when language or hearing barriers exist (AIII)
  • Clinicians should stress the confidential nature of discussions regarding sexual history, mental health, and substance use. (AIII)
  • Clinicians should address the importance of partner notification with HIV-infected patients. HIV and STI testing for partners, including testing for viral hepatitis, should be available onsite.

*As defined by the National Network of Libraries of Medicine [1], health literacy includes the ability to understand prescribing instructions, appointment slips, medical education brochures, doctor’s directions and consent forms and the ability to negotiate complex healthcare systems. Health literacy requires reading, listening, analytical, and decision-making skills, as well as the ability to apply these skills to health situations. More information about health literacy, including a list of resources, is available at: http://nnlm.gov/outreach/consumer/hlthlit.html. Professional development and training for adult education is available through the Literacy Assistance Center.

New York State Law
Clinicians must report confirmed new cases of HIV according to New York State Law and should educate patients with reportable illnesses about the potential for confidential follow-up from the New York State Department of Health or the patient’s local health department (for more information about required reporting, see Provider Reporting and Partner Services).

Detailed information regarding patients’ health, ongoing health risks, and previous HIV treatment should be obtained during the baseline history (see Table 1). This information establishes the framework for ongoing HIV care. Effective communication between the patient and provider is essential for including patients in the decision-making process regarding their medical care (for more information, see the Salzburg Statement on Shared Decision Making [2]). All members of the healthcare team should provide information that is well organized and easy to understand. When language or hearing barriers exist, clinicians should use a professional interpreter or language services.

For patients who have received HIV care from previous providers, past medical records should be obtained whenever possible. The New York State standard consent form is available at: www.health.ny.gov/forms/doh-5032.pdf. Medical records may be available electronically for patients who receive care from providers participating in regional health information organizations (RHIOs). With standardized consent forms signed by patients, providers enrolled in RHIOs are able to share medical information electronically.

KEY POINT
  • Clinical data exchanges, often known as RHIOs (regional health information organizations), continue to expand in New York State. Clinicians should be familiar with RHIOs in their areas and understand the consent procedures used for them. For additional information, refer to the New York eHealth Collaborative (NYeC).

When medical records are not available directly from previous providers, patients may be encouraged to bring their past medical records or any medical information they may have in their possession. However, clinicians should be aware that patients may not wish to disclose to their previous providers that they are changing providers, and fees may be associated with requests for medical records.

Although clinicians may obtain all elements of a comprehensive history during the first few visits to the clinic, it is important to address sexual behavior, mental health, and alcohol and substance use, including illicit use of prescription drugs, during the initial and subsequent clinical encounters. The confidential nature of these discussions should be stressed. Clinicians should note that although the patient may choose not to disclose all pertinent personal information during the first visit, a sympathetic and nonjudgmental attitude can help establish trust and facilitate discussion of these issues during subsequent visits.

Clinicians who are uncomfortable asking questions about substance and alcohol use or sexual risk behaviors should seek training to enhance their comfort level. The NYSDOH Clinical Education Initiative and the NY/NJ AIDS Education Training and Center provide HIV-related educational resources and training for providers. Training in methods of motivational counseling and in prevention interventions, such as Diffusion of Effective Behavioral Interventions, is also available.

Table 1 lists the elements of a comprehensive history and ongoing assessments that are particularly important for HIV-infected patients.

Comprehensive History and Ongoing Assessments for Patients with HIV Infection

Table 1: Comprehensive History and Ongoing Assessments for Patients with HIV Infection
Type Details Frequency
Contact information
  • Patient contact info
  • Patient’s emergency contact info
At each visit
Disclosure of medical information
  • Discuss with the patient 
  • Document patient’s consent to sharing information with contacts
At each visit
Medical history
  • Review sources of past medical care
  • Obtain records whenever possible
  • Past hospitalizations
  • Past surgery(s)
Baseline
Current medical status
  • Recent and current symptoms and illnesses
  • Recent hospitalizations
At each visit
HIV history
  • Date and place of the patient’s diagnosis and route of exposure, if known
  • Most recent viral load and CD4 count
  • Nadir CD4 and peak viral load
ART-related history
  • Current and previous ART regimens
  • Date of initiation of ART
  • Reasons for changes in ART
  • Previous adverse drug reactions, including hypersensitivity reactions to prior therapies such as NNRTIs, ABC, and sulfonamides
  • Challenges with adherence to therapy
  • History of drug resistance if known
Baseline
OI history
  • History of opportunistic infections and malignancies
  • Previous adverse reactions to drugs used for OI prophylaxis 
Baseline
Health literacy
  • Patient’s understanding of HIV disease and treatment
Baseline and at least annually
Partner information

At baseline and whenever a new partner is reported

TB history
  • Possible recent exposure to tuberculosis
  • History of positive TB skin test, commonly known as PPD
  • History of TB disease or treatment of tuberculosis or LTBI
 Baseline and at least annually
Viral hepatitis history
  • HAV infection
  • HBV infection
  • HCV infection
  • Past treatment for HCV
Baseline
Varicella zoster virus history
  • Chickenpox
  • Herpes zoster
Baseline
Medications
  • Current prescription medications
  • Treatment for opioid dependence (methadone and buprenorphine)
  • Hormones
  • OTC agents (NSAIDs, antihistamines, dietary supplements, vitamins)
  • Other nonprescription medicines, including complementary and alternative medicines
Conduct thorough medication history at each visit. (See the Appendix for a Medication Evaluation Form)
Vaccination history
  • Up to date on all recommended vaccinations?
Baseline and at least annually
Reproductive history
  • Pregnancies
  • Births
  • Termination(s) of pregnancy
  • Current contraceptive use and contraceptive needs
  • Preconception planning
Baseline and at least annually
Blood product history
  • Transfusion history
  • Note in particular blood product exposure prior to 1985
Baseline
Chronic medical conditions
  • Hyperlipidemia and cardiovascular disease
  • Peripheral neuropathy 
  • Gastrointestinal disease
  • Diabetes
  • Kidney disease 
  • Note in particular conditions that might affect the choice of ART regimen
Baseline
Neurolocognitive history
  • History of neurocognitive screening
  • Screening results
Baseline
Cancer screening
  • History of cancer
  • History and results of cancer screening
See text below
Allergies
  • History of allergies, allergic reactions
Baseline and at least annually
Place of birth
  • Patient’s place of birth
Baseline
Family medical history
  • Complete family history
  • Family history of chronic medical conditions
  • Family history of cancer
Baseline
Travel history
  • Patient’s travel history
Baseline and at least annually
Other patient info
  • Diet and exercise
  • Education level
  • Occupational history
  • Pets and other animal exposures
  • Baseline
  • Baseline
  • Baseline
  • Baseline and at least annually
Housing
  • Patient’s housing status
  • Names and contact information for housing and case management providers
  • Note: Housing status and contact information should be closely monitored for patients with unstable living situations
Baseline and at least annually
Relationships
  • Patient’s social support
  • Stability of patient’s personal relationships
  • Family and partner contacts
  • People to whom the patient has disclosed his/her HIV status
  • Note: Social support should be closely monitored for patients with unstable living situations
 Baseline and at least annually
Home healthcare
  • Information on past or current home healthcare service use
Baseline and at least annually
Employment and insurance status
  • Patient’s current employment status and employer
  • Insurance status and information
Baseline and at least annually
Gender identity
  • Patient’s gender identity
  • Preferred pronoun
Baseline
Legal issues
  • Living will and healthcare proxy
  • Permanency planning for dependent children
  • Court-related issues (divorce, child custody, immigration status, probation status)
Baseline and at least annually
Coping
  • How is the patient coping with his/her HIV status?
Baseline and at least annually
Mental health history
  • History of or current signs of symptoms of mental illness, including:
  • Depression or other mood disorder
  • Anxiety 
  • Post-traumatic stress disorder 
  • Suicidal/violent behavior 
  • Psychotic disorder
  • Severe and persistent mental illness 
  • History of psychopharmacologic treatment (assess medication adherence if applicable
  • Past psychiatric hospitalizations
Baseline and at least annually
Mental health care provider information
  • Names of and contact information for mental health care providers
Baseline and at least annually
Cognitive function
  • Patient’s cognitive status
Baseline and at least annually

Abuse/violence/
trauma history

  • Past or present experience of violence and trauma
  • Past or present experience of physical abuse
  • Past or present experience with mental abuse
  • Past or present exposure to violence
  • History of abuse during childhood
Baseline and at least annually

History of intimate partner violence

  • Past or present experience with intimate partner violence or abuse
Baseline and at least annually

History of elder abuse

  • In patients aged 65 years or older, history or present experience of elder abuse
Baseline and at least annually

Substances

Substances currently being used or used in the past, including:

  • Tobacco 
  • Alcohol
  • Street drugs: Marijuana, cocaine or crack, heroin, crystal methamphetamine, MDMA/ecstasy, hallucinogens (e.g., LSD, PCP), ketamine
  • Inhalants: Glue, nitrous oxide
  • Prescription drugs used illicitly: Opioids (e.g., Vicodin, codeine), benzodiazepines, amphetamines
Baseline and at least annually

Substance use

  • Frequency of substance use
  • Usual route of administration
Baseline and at least annually

Risk behaviors

History of or currently engaging in risk behaviors, including: 

  • Drug and/or needle-sharing
  • Exchanging sex for drugs (or other transactional sex)
  • Sexual risk-taking while under the influence of drugs or alcohol
Baseline and at least annually

Sexual history

  • Current sexual activity
  • Current and past sex partners
Baseline and at each visit

Sexual risk behavior

  • Sexual practices—vaginal, anal, oral sex
  • Knowledge about and use of latex or polyurethane barriers
Baseline and at least every 4 months

STI history

History of sexually transmitted infections, including:

  • Syphilis
  • Herpes simplex 
  • Genital/rectal warts (HPV)
  • Chlamydial infection
  • Gonococcal infection
  • Chancroid 

See Table 3, Routine Diagnostic Testing and Laboratory Screening for ongoing STI assessment

Sexual function

  • Libido
  • Erectile dysfunction
  • Use of sex-enhancing agents
  • Use of testosterone replacement
Baseline and at least annually

Constitutional symptoms

  • Malaise or fatigue
  • Weakness
  • fevers
  • Night sweats
  • Changes in appetite 
  • Changes in sleep
  • Emotional well-being
At each visit

Pain

  • Scales such as the Wong-Baker Faces Pain Rating Scale or the Numeric Rating Scale may be used
  • Note: Direct questioning about pain is important because patients may not otherwise report symptoms until after they have already caused significant morbidity
At each visit

Vision

  • Change in vision, including blurry vision, double vision, flashes of light, loss of vision, use of glasses, legally blind or blind
Baseline and at least annually

Head, ears, nose

  • Headache
  • Dysphagia
  • Odynophagia
  • Discharge
Baseline and at least annually

Oral 

  • Name and contact information for dental provider and date of last visit
  • Dental pain, denture fit, mastication
Baseline and at least annually

Pulmonary

  • Cough
  • Dyspnea at rest or on exertion
  • Hemoptysis
Baseline and at least annually

Cardiac

  • Chest pain
  • Palpitations
  • Heart murmur
Baseline and at least annually

Abdominal

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Rectal bleeding
  • Rectal pain
  • Hemorrhoids
Baseline and at least annually

Genitourinary

  • Urinary symptoms (dysuria, incontinence, frequency)
  • Vaginal pain
  • OB/GYN: Menstrual status, bleeding, infections, last Pap test and result
  • Perimenopausal or menopausal symptoms
  • History of prostate disorders
Baseline and at least annually

Extremities

Muscle tenderness Baseline and at least annually

Neurologic

Tingling, burning, pain, or numbness in the extremities Baseline and at least annually

Psychosocial Assessment

A psychosocial assessment is used to identify not only the patient’s basic psychosocial information but also circumstances that may require additional services. Important elements of a psychosocial assessment include the following:

  • Stability of housing, employment, government assistance, and level of education
    • Housing status and contact information should be closely monitored for patients with unstable living situations.
  • Support network and safety:
    • Does the patient have contact with family and friends?…Are they aware of the patient’s HIV status?
    • Does the patient have a partner?…Is the patient afraid of his/her partner or someone else close?
  • Whether the patient requires home healthcare
  • Gender identity:
  • Legal issues, including end-of-life arrangements, permanency planning for dependent children, immigration status, probation status
  • How the patient is coping with his/her HIV status

Mental Health and Substance Use Assessment

RECOMMENDATIONS
  • All HIV-infected patients should receive baseline and ongoing assessment for the following (AI):
    • Mental health disorders
    • Depression (every visit)
    • Anxiety (at least annually)
    • Post-traumatic stress disorder (at least annually)
    • Cognitive function (at least annually)
      Sleep habits and appetite assessment (every visit)
    • Alcohol and substance use (at least annually); at-risk drug and alcohol users should be screened more frequently to identify escalation of present levels of use or harmful consequences from use.
    • Suicidal/violent ideation (every visit)
    • Psychosocial status, including domestic violence, family and social support, and housing status (at least annually)
  • Clinicians should use selected brief screening instruments when performing the mental health and substance use assessment. The chosen screening instruments should be tailored for optimal use at initial, annual, and interim visits and adjusted for the patient’s mental health or substance use history. (AIII)
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (AII)

A number of brief screening tools for mental health and substance use assessment are available for use by primary care providers during the history-taking process. For most patients, baseline mental health and substance use screening requires approximately 10-20 minutes. The chosen screening tools should be tailored for optimal use at initial, annual, and interim visits.

When performing substance use screening, clinicians should discuss how alcohol and substance use affect the patient’s health. Judgmental language that can exacerbate stigma, such as “substance abuse” or “alcohol abuse,” should be avoided and screening should be adjusted for the patient’s substance use history.

For additional information regarding mental health and substance use screening and treatment, including mental health and substance use screening questions and instruments, refer to:

For more information regarding neuropsychological assessment, see Neuropsychological Complications. For scripted dialogue for assessing substance use, refer to Substance Use Screening and Ongoing Assessment.

KEY POINT
  • For mental health, substance use, or psychosocial issues that are potential barriers to treatment adherence, clinicians should work with the patient’s case manager to provide necessary medical guidance. When case managers are unavailable, clinicians should refer their patients to social workers who can provide psychosocial services and facilitate referrals to supportive services.

Sexual History

When obtaining a sexual history, terms such as lesbian, homosexual, or gay should be avoided. Questions should relate to the patient’s behavior and not to “sexual identity.” The information derived will be more useful to the clinician and the questions less threatening to many patients. For example, when talking to a male patient, the clinician should ask, Are your sexual partners men, women, or sometimes both? because the patient may not identify with the words “homosexual” or “gay.”

References:
  1. National Network of Libraries of Medicine. Health Literacy. Bethesda, Md. Available at: http://nnlm.gov/outreach/consumer/hlthlit.html
  2. Alambuya RN, Ali S, Apostolidis K, et al.; Salzburg Global Seminar. Salzburg statement on shared decision making. BMJ 2011;342:d1745. [PubMed]

Comprehensive Physical Examination

November 2014

RECOMMENDATION
  • Clinicians should perform a baseline and annual comprehensive physical examination for all HIV-infected patients. All standard elements of a comprehensive physical examination should be performed, with particular attention to areas potentially affected by HIV.

HIV-Related Physical Findings

Except where indicated, each element should be performed at baseline and at least annually. Listed below are elements that warrant particular attention in HIV-infected patients.

Vital signs: Assess at each visit: Blood pressure, pulse, temperature, general appearance, weight, and body mass index

  • Note: General appearance such as body habitus, lipoatrophy (wasting and facial wasting), frailty, weakness, difficulty ambulating, use of ambulatory aides or wheelchair

Skin: Note the following: Psoriasis, molluscum contagiosum, seborrheic dermatitis, nodules/plaques/bruise-like lesions consistent with Kaposi’s sarcoma, tinea, onychomycosis, folliculitis, excoriations, herpes, shingles, drug-related eruptions, skin findings of cirrhosis, signs of violence or abuse (bruising and abrasions), thinning of skin

Lymphatic: Significant abnormalities may present as clusters of large nodes, asymmetry, tenderness, or sudden increases in size or firmness of nodes. Pay particular attention to posterior cervical, cervical, supraclavicular, submental, axillary, epitrochlear, and inguinal node enlargement, tenderness, firmness, drainage, asymmetry

Eyes: Note the following: Icterus, dryness, redness, CMV retinitis, HIV-related retinopathy

  • For asymptomatic patients without significant history and with CD4 counts ≥50 cells/mm3: Follow standard schedule for complete ophthalmic examination for all adults (see Medline Plus for Standard Ophthalmic Examination)
  • For patients with CD4 counts <50 cells/mm3: Complete ophthalmic examination by an ophthalmologist at baseline and every 6 months

Head, ears, nose, throat: Note evidence of sinusitis, hearing loss, or deafness

Oral: Note the following: Oral candidiasis (thrush), hairy leukoplakia (lateral borders of tongue), other leukoplakias, oral carcinoma, lesions, warts, herpes, Kaposi’s sarcoma, gingivitis, periodontitis, tooth loss, tooth decay, dentures, aphthous ulcers, other masses

Neck: Dorsocervical fat pad, masses

Chest and breast: Masses, nipple discharge

Musculoskeletal: Muscle wasting, joint swelling

Genitourinary: Perform complete female pelvic examination and female and male genital examination

  • Note: Vaginal or penile discharge, ulcers, blisters, warts, tenderness, masses, vaginal dryness, cervical abnormalities
  • Related guideline: Gynecological Care

Rectal: Perform rectal examination, including visual inspection and digital rectal examination

Neurologic: Assess gait, cranial nerves, reflexes, and balance and examine for sensory, vibratory, motor, and cerebellar abnormalities; assess mental status (see below, Mental Health and Substance Use)

Elements of the Comprehensive Physical Exam

General Appearance, Vital Signs, and Weight

RECOMMENDATIONS
  • Clinicians should note abnormalities and changes in general appearance, body habitus, physical well-being, frailty, and mobility.
  • Clinicians should assess vital signs, weight, and body mass index (BM) at each visit (see, for instance, CDC Adult BMI calculator).

General appearance and vital signs should be assessed at each visit. Body mass index may be used to tailor patient education and recommendations for weight loss/gain and exercise (refer to Health Promotion and Behavioral Counseling).

KEY POINT
  • Observation of patient’s body habitus and ambulation may detect frailty and decreased mobility, which are increasing as people with HIV age and as more people are diagnosed with HIV at older ages. Weight gain or loss can be the first sign of therapy success or failure, even before laboratory test results are available.

Pain

RECOMMENDATIONS
  • Clinicians should:
    • Ask HIV-infected patients about pain at each visit
    • Use a validated pain scale to track pain over time
    • Document the severity and location of pain and precipitating factors
    • Attempt to identify underlying causes of pain and respond with efforts to alleviate it
    • Provide referral to a pain-management specialist when the patient’s symptoms do not respond to treatment in the primary care setting
  • Clinicians should not deny treatment of pain because of a patient’s past or current history of addiction; clinically appropriate pain management in substance users requires careful individualized judgment (see Pain in the Substance User with HIV Infection).
  • Clinicians should assess patients with chronic pain for fatigue and mental health disorders (see the Mental Health Screening and Somatic Symptoms Guideline).

HIV-infected patients are at increased risk for development of certain painful conditions, particularly neuropathy, which can be due to medications, diabetes, or the underlying HIV infection. Some opportunistic infections are painful, such as chronic herpes simplex virus or varicella zoster virus. Many experts encourage the routine use of pain scales, such as the Wong-Baker Faces Pain Rating Scale or the Numeric Rating Scale, to standardize pain assessments and determine how pain may affect activity and other aspects of function.

Treatment of pain can be complicated if the patient has a history of substance use, and the extended use of opioid analgesics and benzodiazepines may require consultation with substance use treatment professionals. However, no patient should be denied treatment for pain because of a history of substance use. In some cases, it may be useful for the clinician and patient to work together to establish a clear oral or written treatment agreement. For further guidance on treatment agreements and pain management in HIV-infected substance users, refer to Pain in the Substance User with HIV Infection.

Skin

Dermatologic findings, such as rash, lesions of Kaposi’s sarcoma, and vasculitis, may all be the first signs of progression of HIV, comorbid diseases, or toxicities of treatment. Seborrheic dermatitis can be an indicator of immune deficiency. Maceration of the gluteal cleft may not be noticed by the patient but could be a result of Candida infection or herpes simplex virus. Molluscum contagiosum may appear slightly larger and in more clusters in HIV-infected patients and be more widespread. Onychomycosis may involve all fingernails and toenails. Diffuse folliculitis with associated pruritus may occur with immunodeficiency. Spider angiomata or palmar erythema may be signs of cirrhosis.

Examples of dermatologic manifestations of HIV are provided in the appendix, Dermatologic and Related Complications Associated With HIV.

Lymphatic Examination

Generalized lymphadenopathy is a common finding during all stages of HIV disease but does not correlate with prognosis or disease progression. Lymphadenopathy may not be as prominent in older patients.

Reactive lymph nodes may be prominent in early stages of HIV, diminish as disease progresses, and return with immune reconstitution after effective ART has been established. Presentation of asymmetry, clusters of large nodes, or sudden increase in size, firmness, or tenderness of nodes may signal infection, malignancy, or opportunistic infections. Lymph node clusters that are normally quiescent, including posterior cervical chain, submental, supraclavicular, epitrochlear, axillary, and femoral nodes, should not be overlooked.

Eyes: Ophthalmologic Assessment and Referral

RECOMMENDATIONS
  • Patients with CD4 counts <50 cells/mm3 should be examined by an ophthalmologist at baseline and every 6 months. (AIII)
  • Patients with visual disturbances or unremitting ocular symptoms, regardless of CD4 cell count, should be evaluated by an ophthalmologist.(AIII)
  • Asymptomatic patients without a significant history of eye conditions who have CD4 cell counts ≥50 cells/mm3 should receive retinal examinations according to the standard schedule for all adults (see Standard Ophthalmic Examination).

Eye examinations by an ophthalmologist, ideally one experienced with the ocular complications of HIV infection, are important, especially for patients with low CD4 counts who are at higher risk for CMV retinitis resulting from declining immune function. A baseline examination may be indicated for patients with low CD4 counts (<200 cells/mm3) who are initiating ART. This examination should include a dilated funduscopic assessment with indirect ophthalmoscopy.

HIV-infected persons may experience icterus due to atazanavir-containing regimens [1], acute hepatitis due to viruses or medications, or cirrhosis due to chronic viral hepatitis or alcohol abuse.

Head, Ears, Nose, Mouth, Throat, and Neck

RECOMMENDATIONS
  • Clinicians should ascertain whether HIV-infected patients have a regular oral health provider and should refer:
    • Dentulous patients for hygiene and intraoral examinations every 6 months, including screening for dental caries, gum disease, and oral cancer (AIII)
    • Edentulous patients for intraoral examinations annually, including assessment for denture fit and screening for mucosal lesions including oral cancer (AIII)
  • All referrals should be documented in the patient’s medical record.
  • As part of the annual physical examination, clinicians should inspect the patient’s oral cavity.

Clinicians should make a dental referral for every HIV-infected patient under their care. The patient’s access to regular and urgent dental care should be identified. As part of the annual physical examination, the clinician should visually examine and palpate the patient’s lips, labial and buccal mucosa, all surfaces of the tongue and palate, and the floor of the mouth. The gingiva should be examined for signs of erythema, ulceration, or recession. Numerous HIV-related diseases may present with oral manifestations. Leukoplakias associated with tobacco use and HPV exposure are common; oral hairy leukoplakia, while uncommon, may also be present. Kaposi’s sarcoma and lymphoma may first occur in the face, mouth, throat, or neck. 

Although HIV infection itself does not increase the likelihood of upper respiratory infections, sinusitis and otitis occur more frequently in the HIV-infected population and can be severe and chronic.

An increased dorsocervical fat pad is a common manifestation of lipodystrophy. Although primarily a cosmetic concern, prominent dorsocervical fat pads may cause significant distress and depression, increase stigma associated with HIV/AIDS, limit neck mobility, and be associated with back pain.

Respiratory/Chest

The evaluation of respiratory symptoms in HIV-infected patients can be challenging because those symptoms may be due to a broad spectrum of illnesses that may or may not be related to HIV. HIV-related conditions comprise a wide range of infections, including neoplasms and opportunistic infections such as pneumonia, pleural effusion, and empyema. Symptoms may include chest pain, dyspnea, cough, pleurisy, and hemoptysis. Chronic lung disease is increasingly common among people with HIV infection due to smoking, aging, and improved survival after Pneumocystis jirovecii pneumonia (PCP). The prevalence of smoking among HIV-infected patients is 2- to 3-fold higher than that of the general population [2].

KEY POINT
  • The risk of mortality associated with smoking has been found to be significantly increased among HIV-infected patients (61.5%) compared with those not infected with HIV (34.2%) [3].

Evidence also suggests that lung cancer may be increased in HIV infection independent of smoking history [4-6]. Pulmonary hypertension can cause respiratory symptoms and is increased in patients with HIV, especially those with untreated advanced HIV/AIDS.

Cardiovascular

Untreated or inadequately suppressed HIV infection is associated with increased risk of myocardial infarction and stroke; this may be related to inflammatory responses due to an induced state of chronic immune activation [7-9], as well as lower CD4 counts [10,11] and higher viral load levels [7].Although the risk of cardiovascular disease may be reduced with ART compared with untreated HIV, metabolic complications, including cardiovascular disease, have been associated with long-term HIV treatment [12-14]. Older nucleoside reverse transcriptase inhibitors (e.g., zidovudine, didanosine) may cause cardiomyopathy [15]; however, this effect is rare.

Injection drug users are at increased risk for endocarditis and mycotic pseudoaneurysms [16]. A number of complications of advanced HIV disease or AIDS can involve the cardiovascular system. Tuberculosis, CMV, toxoplasmosis, lymphoma, and other opportunistic infections and cancers can involve the heart or blood vessels. Manifestations include myocarditis, pericardial effusion, chronic heart failure, cardiomyopathy, and vasculitis.

Gastrointestinal

Hepatosplenomegaly may be caused by infection, medications, alcohol, or other infiltrative disease processes. Certain combinations of antiretroviral agents may increase the likelihood of finding multiple lipomata in the subcutaneous fat. Increased visceral fat associated with ART may cause abdominal distension, requiring radiologic imaging to evaluate for other processes such as ascites. Chronic hepatitis B and C infection increase the risk of hepatocellular cancer, cirrhosis, portal hypertension, encephalopathy, coagulopathy, and ascites. Tuberculosis, lymphoma, Kaposi’s sarcoma, CMV, and other conditions can involve abdominal structures. Increased rates of pancreatitis are found with excessive alcohol use [17].

Genitourinary

RECOMMENDATIONS
  • Clinicians should examine all HIV-infected patients for anogenital ulcerative lesions.
  • Clinicians should perform a gynecologic examination in all HIV-infected women or refer them to a gynecologist at baseline and at least annually.
  • At baseline and as part of the annual physical examination for all HIV-infected adults, regardless of age, clinicians should:
    • Inquire about rectal symptoms, such as itching, bleeding, discharge, diarrhea, or pain
    • Perform a visual inspection of the perianal region
    • Perform a digital rectal examination
  • Clinicians should refer any patient with abnormal anal physical findings, such as warts, hypopigmented or hyperpigmented plaques/lesions, lesions that bleed, or any other lesions of uncertain etiology, for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
  • Transgender patients should receive a genitourinary examination according to standards of care for their anatomy. Male-to-female transgender patients with a neo-vagina should receive pelvic examinations according to HIV care guidelines for natal females. Before performing a pelvic examination, the clinician should explain the medical reasons for the examination (see Care of the HIV-Infected Transgender Patient). (AIII)

Because patients may be reluctant to report signs or symptoms of sexually transmitted infections (STIs) or other genital abnormalities, clinicians should carefully inspect the anogenital area for discharge and ulcerative lesions, including lesions associated with HPV, syphilis, and classic genital herpes simplex virus (HSV), as well as atypical HSV presentations, such as nonhealing gluteal cleft maceration.

In addition to a genital examination, a careful pelvic examination is essential for natal women, as well as male-to-female women who have a neo-vagina.

During the rectal examination, evidence of skin abnormality around the anus should be referred for high-resolution anoscopy (HRA) and/or examination with biopsy of abnormal tissue. For additional information, see Anal Dysplasia and Cancer.

As people with HIV age, increasingly important issues include sexual dysfunction, prostate health, and peri- and postmenopausal illness.

Neuropsychological Examination

RECOMMENDATIONS
  • As part of the routine mental health assessment for HIV-infected patients, clinicians should assess cognitive function (see Mental Health and Substance Use).
  • Clinicians should assess gait, cranial nerves, reflexes, and balance in HIV-infected patients, as well as examine for sensory, vibratory, motor, and cerebellar abnormalities.
  • Clinicians should refer HIV-infected patients with more complex suspected or proven peripheral neuropathy syndromes to a neurologist to assist with the diagnosis and management.

HIV-related neurologic changes can occur, even without the neurologic side effects of medications, especially as HIV disease progresses. For further information, including screening tools for cognitive impairment, see Cognitive Disorders Guideline.

Physical and occupational therapists may provide assessment and collaborative management for patients with frailty, balance and sensory deficits, and pain.

References:
  1. Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-containing antiretroviral regimens, with or without ritonavir, in patients who are HIV-positive and treatment-naïve. Pharmacotherapy 2013;33:284-294. [PubMed]
  2. Rahmanian S, Wewers ME, Koletar S, et al. Cigarette smoking in the HIV-infected population. Proc Am Thorac Soc 2011;8:313-319. [PubMed]
  3. Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: A nationwide, population-based cohort study. Clin Infect Dis 2013;56:727-734. [PubMed]
  4. Sigel K, Wisnivesky J, Gordon, et al. HIV as an independent risk factor for incident lung cancer. AIDS 2012;26:1017-1025. [PubMed]
  5. Mani D, Haigentz M Jr, Aboulafia DM. Lung cancer in HIV infection. Clin Lung Cancer 2012;13:6-13. [PubMed]
  6. D’Jaen GA, Pantanowitz L, Bower M, et al. Human immunodeficiency virus-associated primary lung cancer in the era of highly active antiretroviral therapy: A multi-institutional collaboration. Clin Lung Cancer 2010;11:396-404. [PubMed]
  7. Zhang S, van Sighem A, Kesselring A, et al. Episodes of HIV viremia and the risk of non-AIDS diseases in patients on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr 2012;60:265-272. [PubMed]
  8. Gordin F, Finley E, Dietz D, et al.; Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008;197:1133-1144. [PubMed]
  9. El-Sadr WM, Lundgren J, Neaton JD, et al.; Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355:2283-2296. [PubMed]
  10. Phillips AN, Carr A, Neuhaus J, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: Exploratory analyses from the SMART trial. Antivir Ther 2008;13:177-187. [PubMed]
  11. Lichtenstein KA, Armon C, Buchacz K, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study.Clin Infect Dis 2010;51:435-447. [PubMed]
  12. Mocroft A, Phillips AN, Gatell J, et al. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use. AIDS 2013;27:907-918. [PubMed]
  13. Friis-Møller N, Thiébaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: The data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil 2010;17:491-501. [PubMed]
  14. May M, Sterne JA, Shipley M, et al. A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men. Int J Epidemiol 2007;36:1309-1318. [PubMed]
  15. Frerichs FC, Dingemans KP, Brinkman K. Cardiomyopathy with mitochondrial damage associated with nucleoside reverse-transcriptase inhibitors. N Engl J Med 2002;347:1895-1896. [PubMed]
  16. Arora S, Weber MA, Fox CJ, et al. Common femoral artery ligation and local debridement: A safe treatment for infected femoral artery pseudoaneurysms. J Vasc Surg 2001;33:990-993. [PubMed]
  17. Herreros-Villanueva M, Hijona E, Bañales JM, et al. Alcohol consumption on pancreatic diseases. World J Gastroenterol 2013;19:638-647. [PubMed]

Laboratory and Diagnostic Testing

March 2011

RECOMMENDATION
  • Clinicians should order appropriate laboratory assessments and screening tests for management of HIV-infected patients (see Table 3). (III)
Table 3: Routine Laboratory Testing and Diagnostic Screening
Assessment Diagnostic Screen and Frequency Comments
Virologic assessment
  • Quantitative HIV RNA testing for viral load assessment; the same testing laboratory should be used; recommended intervals differ based on length of suppression, CD4 count, and general adherence to medical care, including visit attendance
  • Resistance testing: Baseline, regardless of whether ART is being initiated (genotypic testing) and prior to initiating treatment in ART-naïve patients (genotypic testing) and when patients experience virologic failure or incomplete viral suppression while receiving ART (genotypic and/or phenotypic testing
  • The initial test performed in an ART-naïve individual should be an assay that can document a potentially high viral load level.
  • All patients with a viral load <400 copies/mL should be retested with an assay that can detect <50 copies/mL; the same testing laboratory and the same assay should be used thereafter.
  • For additional information regarding genotypic and phenotypic testing, refer to Monitoring Patients on ART
Immunologic assessment

CD4 lymphocyte count and percentage: To produce reliable results, the same testing laboratory should be used; recommended intervals differ based on clinical stability and level of virologic suppression

Tuberculosis evaluation
  • For patients with no previous history of TB or no previous positive TST: TST or other FDA-approved test baseline and annually
  • For patients known to have a history of TB or known to be TST positive: Chest X-ray baseline and annually
  • Tuberculin skin test, commonly known as PPD.
Screening for STIs

RPR or VDRL for syphilis:

  • Verify positive test by confirmatory FTA-Abs or TP-PA
  • Baseline and at least annually
  • Every 3 months for patients with continued high-risk behavior

Gonorrhea and chlamydia:

  • Sexually active women <25 years of age
  • Women ≥25 years of age with risk factors
  • All HIV-infected men with ongoing high-risk behavior
  • Baseline and at least annually
  • Patients who continue to engage in unsafe sexual practices are at increased risk for other STIs. Patients with any other STIs, whether ulcerative or not, are at higher risk for HIV transmission. Recent increases in STIs among men who have sex with men warrant screening of asymptomatic sexually active patients [1] 
  • All sites of possible exposure are screened. For specific recommendations regarding the types of assays used, refer to Gonococcal and Chlamydial Infections. 
  • Risk factors for women ≥25 years of age include one of the following: recent STI, having multiple sexual partners, having had a new sexual partner, or having a sexual partner with symptoms of an STI.
Cytologic Screening
  • Cervical Pap tests: Baseline; 6 months after baseline, then annually as long as results are normal
  • Anal Pap tests for men who have sex with men, any patient with a history of anogenital condylomas, women with abnormal cervical/vulvar history: Baseline and annually
  • Colposcopy should be performed for all HIV-infected women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis.
  • Abnormal Pap tests should be repeated every 3 to 6 months thereafter until there have been two successive normal cervical Pap tests.
  • Women with cervical HSIL also should be referred for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
Hematologic assessment

Complete blood count, including differential: Baseline and at least every 4 months

Renal assessment
  • Urinalysis, total protein, and albumin: Baseline and at least annually
  • Serum creatinine and calculated glomerular filtration rate (GFR): Baseline and at least every 6 months
  • Blood urea nitrogen (BUN): Baseline and at least every 6 months
For patients receiving a tenofovir-containing regimen, clinicians should estimate glomerular filtration rate at initiation of therapy, 1 month after initiation of therapy, and at least every 4 months thereafter.
Metabolic assessment
  • Fasting blood glucose for patients receiving ART: Before initiating ART; 3 to 6 months after initiating; annually thereafter
  • Fasting lipid profile, including cholesterol for patients not receiving ART: At baseline and annually
Hepatic assessment
  • Hepatitis A serology: For patients at risk for HAV infection or HAV-related morbidity or mortality 
  • Hepatitis B serology: Baseline
  • Hepatitis C serology: Baseline; baseline and annually for patients at risk 
  • Serum liver enzymes: Baseline and at least every 4 months for patients receiving ART
  • A qualitative HCV RNA PCR should be obtained when no hepatitis antibodies are detectable in a patient with elevated serum liver enzymes and risk factors for HCV.
  • HIV-infected patients who are seronegative for HCV but have continued high-risk behaviors should be screened at least annually for HCV.
  • Individuals at high risk include injection drug users, men who have sex with men without barrier protection, or anyone with multiple sexual partners.
Additional tests
  • Amylase and lipase testing: Baseline
  • Toxoplasma gondii antibody screening: Baseline
  • Varicella antibody screening for adults without a history of chickenpox: Baseline
  • Depending on the patient’s history, these additional baseline tests may be needed.

Virologic Assessment

RECOMMENDATIONS
  • Clinicians should use an assay with a high upper limit of detection (e.g., ≥750,000 copies/mL) for initial measurement of HIV viral load in ART-naïve patients. (III)
  • Clinicians should obtain viral load before vaccinations and not during intercurrent illness because these situations may lead to a transient elevation in viral load. (III)
  • Clinicians should perform resistance testing under the following circumstances:
    • At baseline, regardless of whether ART is being initiated (genotypic testing)
    • In ART-naïve patients before initiation of ART (genotypic testing)
    • In patients experiencing treatment failure or incomplete viral suppression while receiving ART (genotypic and/or phenotypic testing)
  • Clinicians should seek expert consultation for interpretation of genotypes. (III)

There are several methods of measuring HIV viral load levels (e.g., PCR, bDNA, NASBA), each with different ranges (e.g., standard, ultrasensitive). The same assay should be used consistently to avoid confusion.

The initial test performed in an ART-naïve individual should be an assay that can document a potentially high viral load level. All patients with a viral load <400 copies/mL should be retested with an assay that can detect ≤50 copies/mL. Newer assays have a greater dynamic range than either the standard or ultrasensitive assay (e.g., 40 to 10,000,000 copies/mL). The range of detection for the standard PCR assay is 400 to 750,000 copies/mL, whereas the range for the ultrasensitive assay is 50 to 75,000 copies/mL.

KEY POINT

Regular monitoring of HIV RNA levels remains the most meaningful measure of effective ART (for recommended intervals, see Virologic and Immunologic Monitoring).

Resistance testing should be performed 1) at baseline in the setting of acute infection, regardless of whether ART is being initiated (genotypic testing); 2) prior to initiating treatment in ART-naïve patients to determine whether they are infected with drug-resistant virus (genotypic testing); and 3) in patients experiencing virologic failure or incomplete viral suppression while receiving ART (genotypic and/or phenotypic testing). Most currently available assays require a viral load level of >500 to 1000 copies/mL for detection. For more information regarding resistance testing, refer to  HIV Resistance Assays.

Immunologic Assessment

RECOMMENDATION

The CD4 lymphocyte profile should include both the absolute count and percentage. (I)

A decline in absolute CD4 count may occur in some situations, such as after interferon therapy, when all lymphocyte populations are suppressed; however, the percentage of CD4 lymphocytes will remain relatively constant. A stable CD4 percentage generally indicates stable immune function even in the presence of declining absolute counts.

KEY POINT

Routine quarterly monitoring of CD4 count is no longer recommended for nonpregnant patients receiving ART who have consistently undetectable HIV RNA levels and CD4 counts >200 cells/mm3 (for recommended intervals, see Virologic and Immunologic Monitoring).

Tuberculosis Evaluation

RECOMMENDATIONS
  • Clinicians should obtain a TST (tuberculin skin test, commonly known as PPD) or other FDA-approved test for diagnosis of latent tuberculosis infection, unless the patient has previously tested positive or has had previously documented TB. (I)
  • After active tuberculosis has been excluded, clinicians should prescribe TB prophylaxis when a TST results in induration of ≥5 mm or when another FDA-approved test indicates the presence of latent TB infection. (I)

Induration of ≥5 mm with a TST (tuberculin skin test, commonly known as PPD) is considered a positive reaction in the HIV-infected population and warrants prophylaxis. In general, anergy testing is no longer recommended [2].

Laboratory Screening for Sexually Transmitted Infection

RECOMMENDATIONS
  • Clinicians should screen HIV-infected patients for syphilis by obtaining a non-treponemal test (RPR or VDRL) with verification of reactive test by confirmatory fluorescent treponemal antibody absorbance (FTA-Abs) or treponema pallidum particle agglutination (TP-PA) tests at baseline and at least annually. Patients with continued high-risk behavior should be screened for syphilis every 3 months.
  • Clinicians should screen sexually active HIV-infected women under the age of 25 for gonorrhea and chlamydia at baseline and at least annually. Clinicians should screen all sites of possible exposure, including the cervix, rectum, and pharynx. Culture or nucleic acid amplification tests (NAT) should be used to screen for gonorrhea. Immunofluorescence or DNA amplification should be used for chlamydia.
  • Clinicians should screen women 25 years of age or older for gonorrhea and chlamydia at baseline and at least annually if they have or have had a recent sexually transmitted infection, have multiple sexual partners, have had a new sexual partner, or have a sexual partner with symptoms of an STI.
  • Clinicians should screen all HIV-infected men with ongoing high-risk sexual behaviors for gonorrhea and chlamydia at baseline and at least annually. Clinicians should screen all sites of possible exposure, including the urethra, rectum, and pharynx.
  • Clinicians must report all suspected or confirmed syphilis, chancroid, gonococcal, and chlamydial infections to the local health department of the area where the patient resides according to NYS requirements (also see Communicable Disease Reporting Requirements).

The FTA-Abs and TP-PA confirmatory tests remain positive for life if there has been a history of syphilis infection. Some individuals previously treated for syphilis will continue to have a low serum antibody-positive RPR or VDRL. A 4-fold increase in RPR serum antibody indicates acute infection or re-infection with syphilis.

Cytological Screening

Cervical Pap Tests
RECOMMENDATIONS
  • Clinicians should obtain cervical Pap tests for all HIV-infected women at baseline, 6 months after baseline, and then repeat annually, as long as results are normal.
  • Colposcopy should be performed for women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis.
  • Clinicians should repeat abnormal Pap tests every 3 to 6 months thereafter until there have been two successive normal cervical Pap tests. Women with cervical HSIL also should be referred for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
  • Clinicians should obtain at least an annual Pap test in HIV-infected women who have undergone either a supracervical or total hysterectomy.

The purpose of cervical screening is to prevent the development of invasive cancer by identifying and treating individuals with precursor lesions that are at risk for progression to cancer. Widespread screening of all women with cervical cytology or Pap tests has led to a decline in morbidity and mortality from cervical cancer. The benefit of screening and treatment protocols for cervical abnormalities in HIV-infected women is also well established. Although cervical cytology (Pap tests) has lower sensitivity compared to actual tissue histology, colposcopy with Pap tests has increased the effectiveness of the evaluation of women with HIV infection, particularly those women with a report of atypical squamous cells of undetermined significance (ASC-US) by delineating likely abnormal tissue for biopsy and histologic evaluation [3].

Recurrent dysplasia on the vaginal cuff can be seen in women with a history of cervical dysplasia, and both HIV and HPV infections increase the risk of vaginal intraepithelial neoplasia. Therefore, women who have undergone a hysterectomy should still receive annual Pap tests. For additional information, see Cervical Cancer and Dysplasia.

Anal Pap Tests
RECOMMENDATIONS
  • Clinicians should obtain anal cytology at baseline and annually in the following HIV-infected populations:
    • Men who have sex with men
    • Any patient with a history of anogenital condylomas
    • Women with abnormal cervical/vulvar histology
  • Clinicians should refer patients with abnormal anal cytology for high-resolution anoscopy and/or examination with biopsy of abnormal tissue. (III)

Like cervical cancer, invasive squamous cell cancers of the anal canal are associated with certain types of human papillomavirus (HPV) infection, most notably, HPV-16 and HPV-18. Although this is a new practice that may not be routinely available, screening for cellular dysplasia is prudent and recommended, particularly in persons at high risk for infection with papilloma viruses. For additional information, see Anal Dysplasia and Cancer.

References:
  1. Palefsky J, Holly E, Ralston M, et al. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J Infect Dis 2001;183:383-391. [PubMed]
  2. Centers for Disease Control and Prevention. Anergy skin testing and tuberculosis preventive therapy for HIV-infected persons: Revised recommendations. MMWR Morb Mortal Wkly Rep 1997;46(RR-15):1-10. [PubMed]
  3. Franco EL, Duarte-Franco E, Ferenczy A. Cervical cancer: Epidemiology, prevention and the role of human papillomavirus infection. CMAJ2001;164:1017-1025. [PubMed]

Health Promotion and Behavioral Counseling

March 2007

RECOMMENDATION
  • Clinicians should provide routine HIV risk-reduction counseling and behavioral health counseling for HIV-infected patients. (I)

Patients’ behaviors change over time as the course of their disease changes and their social situations vary. The clinician will need to tailor routine risk-reduction counseling and behavioral health counseling not only to the individual patient but also to the particular point in time in the patient’s life [1].

Elements of Health Promotion and Behavioral Health Counseling

Safer sex practices: 

  • Partner notification
  • Latex and polyurethane barriers
  • Behaviors that carry transmission risk and those that do not

Substance use:

  • Counseling if indicated based on assessment: Brief interventions and/or motivational interviewing; harm-reduction counseling; referral for treatment (see Working With the Active User)
  • For injection drug users: Safe injection practices; safe disposal of sharps; access to sterile injecting equipment

Tobacco use: Smoking cessation education

Reproductive health counseling: 

  • Family planning
  • Options for the HIV-infected pregnant women
  • HIV transmission prevention
  • Risk of HIV transmission through breastfeeding [24]

Psychosocial assessment: 

  • Housing status
  • Employment and insurance
  • Educational level
  • Family and partner contacts
  • Stability of personal relationships; domestic violence screening
  • Legal issues: Living will and healthcare proxy; permanency planning for dependent children

Diet and exercise: Nutrition and exercise counseling; diabetes and lipid abnormality counseling

Safer Sex Education

RECOMMENDATIONS
  • Clinicians should discuss safer sexual practices with HIV-infected patients on a routine and ongoing basis. (I)
  • Clinicians should routinely discuss with patients the importance of disclosure to partners. Patients should be educated about the options for voluntary partner notification. These discussions should be clearly documented. Information about HIV reporting and partner notification in New York State is available at Provider Reporting & Partner Services. (I)
  • Clinicians should emphasize that transmission of HIV may occur during unprotected sex, even when patients have undetectable HIV plasma viral loads. (I)
  • Clinicians should recommend the correct and consistent use of latex or, when latex allergies exist, polyurethane male condoms and should discuss the option of using polyurethane female condoms. (I)
  • Clinicians should instruct patients in the proper use of condoms, dental dams, and other barriers to reduce the risk of HIV transmission. (I)
  • Clinicians should educate their patients to avoid using condoms and creams containing nonoxynol-9. (I)

For patients who are sexually active, discussion should include a review of safer practices to prevent the transmission of HIV or other STIs. It is important to note that risk for transmission of HIV is increased in the setting of STIs, underscoring the importance of correct and consistent use of barrier protection during vaginal, rectal, or oral intercourse. Patients should be informed that because condoms do not cover all exposed areas, they are more effective in preventing infections transmitted by fluids from mucosal surfaces than in preventing infections transmitted by skin-to-skin contact.

The use of both male and female condoms among patients should be encouraged, despite adverse attitudes toward them in some communities. Condoms should be offered along with instructions, support, counseling, and referral to community-based organizations.

Clinicians should also inform patients that condoms containing nonoxynol-9, a topical spermicide used to prevent conception, should be avoided. In at least one large placebo-controlled study of sex workers using nonoxynol-9, there was an increase in new HIV infection [3].

Substance Use Counseling

RECOMMENDATIONS
  • When current alcohol or other substance use is identified, clinicians should discuss the possible effects of such use on the patient’s general health and HIV medications, as well as options for treatment if indicated. These discussions should be properly documented in the patient’s chart. (I)
  • Clinicians should evaluate for possible interactions among illicit drugs and prescription drugs. (I)
  • Clinicians should issue prescriptions for new needles and syringes to patients who inject drugs.
  • Clinicians should discuss with patients other options for accessing new needles and syringes, including use of the Expanded Syringe Access Program and Syringe Exchange Programs, New York State’s two syringe access initiatives. (I)
  • Clinicians should collaborate with social work staff and other mental health providers, when available, to determine which treatment programs or substance use services best meet the patient’s needs. (I)

The guidelines on HIV and substance use contain information on the management of HIV-infected substance users. For specific information regarding interactions between illicit drugs and prescription drugs, refer to Drug-Drug Interactions Between Antiretroviral Agents, Medications Used in Substance Use Treatment, and Recreational Drugs.

Tobacco Use Assessment and Counseling

RECOMMENDATION
  • Clinicians should assess smoking status and should encourage those who smoke to stop (I). Pharmacotherapy and referrals to smoking cessation programs should be provided if the patient is interested.

Smoking increases a patient’s risk of developing thrush, cryptococcal meningitis, bacterial pneumonias, and coronary artery disease. In addition, HIV infection further increases the risk of lung and other cancers associated with smoking.

Smoking cessation interventions delivered during routine visits will reach many smokers who are already receiving care for their HIV infection. Patients who are interested in quitting smoking within the next month should be helped to set a quit date, offered pharmacotherapy with nicotine replacement or bupropion, and referred to a counseling program. For further guidance on smoking cessation, refer to Smoking Cessation in HIV-Infected Patients.

Reproductive Counseling

RECOMMENDATION
  • Clinicians should discuss family planning with patients, including risks to the mother and fetus during pregnancy.

Many patients have questions about having children even though they or their partners are infected with HIV. Risks to the mother and fetus, as well as the risk of HIV transmission through breastfeeding [2], should be discussed. Alternative or supplemental family planning methods beyond condom use may also be addressed.

For additional information, refer to Preconception Care for HIV-Infected Women.

Domestic Violence

RECOMMENDATIONS
  • Clinicians or a member of the healthcare team should screen all male and female HIV-infected patients for current and lifetime domestic violence at baseline and annually. (I)
  • Prior to screening patients for domestic violence, clinicians should discuss confidentiality and exceptions to confidentiality, including instances of suspected child abuse and maltreatment and intent to harm self or others.
  • Domestic violence screening should be performed only when the patient is alone.

When real or potential domestic violence is recognized, social work services should be involved and referrals should be made to domestic violence organizations or domestic violence counseling. In the absence of social work services, clinicians should be familiar with resources available in the community and mechanisms of referral.

The following are questions that may be used for screening:

  1. Do you ever feel unsafe at home?
  2. Are you in a relationship in which you have been physically hurt or felt threatened?
  3. Have you ever been or are you currently concerned about harming your partner or someone close to you?

Other questions regarding sexual abuse, such as forced sexual activity, coercion, etc., may be applicable depending on the case.

For more information regarding assessment for domestic violence, refer to the New York State Office for the Prevention of Domestic Violence.

Psychosocial Assessment

RECOMMENDATIONS
  • The clinician or a member of the healthcare team should perform a psychosocial assessment of HIV-infected patients, including housing status, at baseline and at least annually. (I)
  • The clinician should work with the patient’s case manager to provide necessary medical guidance related to psychosocial issues that are potential barriers to treatment adherence. (I)

When case managers are unavailable, clinicians will need to be able to refer their patients to social workers who can provide psychosocial services and facilitate referrals to supportive services. See above for elements of a psychosocial assessment.

Diet and Exercise Counseling

Diet and exercise counseling can enhance the management of and the patient’s knowledge about the risks associated with diabetes, hypertension, problems associated with lipid abnormalities, and potential side effects of medications.

References:
  1. Schreibman T, Friedland G. Human immunodeficiency virus infection prevention: Strategies for clinicians. Clin Infect Dis 2003;36:1171-1176. [PubMed]
  2. Committee on Pediatric AIDS. Infant feeding and transmission of human immunodeficiency virus in the United States. Pediatrics 2013;131;391-396. [PubMed]
  3. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 2002;360:971-977 (Erratum in: Lancet 2002;360:1892). [PubMed]

Preventive Medicine

March 2011

Standard Health Maintenance

RECOMMENDATIONS
  • Clinicians should discuss general preventive healthcare and health maintenance with all HIV-infected patients routinely and, at a minimum, annually. (I)
  • Clinicians should perform standardized age- and sex-appropriate health-maintenance interventions, such as cancer screening, in HIV-infected patients according to the same guidelines used for non-HIV-infected patients (see text). (I)
  • Clinicians should instruct patients on how to perform breast and testicular self-examinations. (III)

Age-Appropriate Diagnostic Screening

Mammogram: Annually for women aged ≥40

Prostate-specific antigen (PSA): Annually, with digital rectal exam, for men aged ≥50 with at least a 10-year life expectancy

  • Annually for men aged ≥45 who are African American or who have a father, brother, or son who was diagnosed with prostate cancer at a young age

Colorectal cancer screen: Although the optimal screening strategy has not been established, one of the colorectal cancer screens listed below should be used. 

  • Screen at age ≥50 
  • Screening African Americans at age ≥45 may be advisable. African Americans have a younger mean age of onset of colorectal cancer and a greater incidence of cancerous lesions in the proximal large bowel [1].
  • Colonoscopy every 10 years or
  • Annual fecal occult blood testing (FOBT) with flexible sigmoidoscopy every 5 years or
  • Annual FOBT and double-contrast barium enema every 5 years

Colorectal cancer is the second leading cause of cancer death in the United States. According to the United States Preventive Services Task Force, universal screening for colorectal cancer in the general population should begin at age 50 in the absence of specific risk factors, such as previous colorectal cancer, strong family history, familial polyposis, or inflammatory bowel disease. Some data support screening African Americans aged ≥45 because they have a younger mean age of onset of colorectal cancer compared with other groups and a greater incidence of cancerous lesions in the proximal large bowel [1].

Opportunistic Infection Prophylaxis

RECOMMENDATION
  • Clinicians should initiate prophylaxis for specific opportunistic infections as indicated in Table 4 and discontinue it as indicated in Table 5. (I)

Prophylaxis for opportunistic infections may be withdrawn for patients who are on effective ART and who have evidence of recovery of immunologic competence.

Table 4: Initiation of Primary OI Prophylaxis 
Pathogen Initiate Prophylaxis Preferred Agent Alternative Agents

Pneumocystis jirovecii pneumonia 

(formerly Pneumocystis carinii)

CD4 <200 cells/mm3 or <14% or a history of oropharyngeal candidiasis TMP/SMX
qd or 3x/week
  • Dapsone*
  • Dapsone* + pyrimethamine + leucovorin
  • Atovaquone
  • Aerosolized pentamidine
Mycobacterium avium complex (MAC) CD4 <50 cells/mm3
  • Azithromycin
  • Clarithromycin
  • Rifabutin
  • Azithromycin + rifabutin
Toxoplasma encephalitis (TE) CD4 <100 cells/mm3 and Positive serology for Toxoplasma (IgG+) TMP/SMX qd
  • Dapsone* + pyrimethamine + leucovorin
  • Atovaquone with or without pyrimethamine + leucovorin
Cytomegalovirus (CMV) Not routinely recommended NA NA
Cryptococcus neoformans Not routinely recommended NA NA
Candida Not routinely recommended NA NA

*Screen for G6PD deficiency before initiating dapsone.

Table 5: Discontinuation of OI Prophylaxis
Pathogen Discontinuation of Primary Prophylaxis Discontinuation of Secondary Prophylaxis
Pneumocystis jirovecii pneumonia (PCP) Patient receiving ART with increase in CD4 to >200 cells/mm3 for ≥3 months
  • CD4 count >200 cells/mm3 for ≥3 months in response to ART
  • Adequate viral suppression
  • If PCP occurred with CD4 >200 cells/mm3, prophylaxis should be maintained
Toxoplasma encephalitis (TE) [a] Patient receiving ART with increase in CD4 to >200 cells/mm3 for ≥3 months
  • CD4 >200 cells/mm3 for ≥6 months in response to ART
  • Completed initial therapy
  • Asymptomatic for TE
Mycobacterium avium complex (MAC) CD4 increase to >100 cells/mm3 for ≥3 months in response to ART
  • CD4 increase to >100 cells/mm3 for ≥6 months in response to ART
  • Completed at least 12 months of treatment for disseminated MAC [b]
  • Asymptomatic for MAC
Cryptococcosis N/A
  • CD4 increase to >100 to 200 cells/mm3 for ≥6 months
  • Completed initial therapy
  • Asymptomatic for cryptococcosis
Cytomegalovirus (CMV) N/A
  • CD4 >100 to 150 cells/mm3 for ≥6 months
  • No evidence of active disease
  • Regular ophthalmologic examination
  1. HIV-infected adults or adolescents with a history of toxoplasmosis in childhood should be administered lifelong prophylaxis to prevent recurrence.

  2. Obtaining blood cultures or bone marrow cultures may be advisable to ascertain disease activity.

Immunizations

Note
The immunizations information in this section is outdated and currently under revision. Please refer to the Centers for Disease Control and Prevention Adult Immunization Schedules for the most current recommendations regarding standard and HIV-related vaccinations.

The potential danger from live virus vaccinesImmunizations against infectious diseases are an extremely important component of care for patients with immune suppression. Concerns regarding vaccinations in HIV-infected individuals include:

  • The ability of HIV-infected patients to mount an appropriate immune response to vaccine

In general, the more intact the immune system is, the more effective and safe the vaccines are. The use of live virus vaccines is generally undertaken when an inactivated version does not exist and when the risk of the disease clearly outweighs the theoretical risk of vaccination.

2016 Health Alert
See New York State Department of Health recommendations for information regarding vaccination against meningococcal disease for men who have sex with men.
References:
  1. Agrawal S, Bhupinderjit A, Bhutani MS, et al.; for the Committee of Minority Affairs and Cultural Diversity, American College of Gastroenterology. Colorectal cancer in African Americans. Am J Gastroenterol 2005;100;515-523. [PubMed]

Coordination of Care and Services

March 2007

RECOMMENDATIONS
  • As part of the initial visit, the clinician or other member of the healthcare team should educate new patients about the following items (III):
    • How to access emergency services (provide a phone number for 24-hour services)
    • Whom to contact to schedule appointments
    • How to obtain laboratory and radiology results, medical records, and other reports
  • After receiving patient consent, clinicians should share information with other agencies from which their patients are receiving services. (III)
  • Case management should be used to enhance coordination of care provided by agencies such as home care, nutrition services, and nursing services and to prevent duplication of services. (III)
  • Clinicians should regularly involve case managers in case conferences to discuss psychosocial issues that may affect a patient’s ability to adhere to care. (III)

Comprehensive HIV care often involves multidisciplinary care with involvement of more than one provider. To facilitate adherence to all facets of care, the clinician should work with the case management team to coordinate medical care, referrals, and ongoing services in the community.

Appropriate Use of Acute Care Services

RECOMMENDATIONS
  • Outpatient clinicians who do not provide inpatient care should have a network of practitioners with whom they can communicate easily should their patients require hospitalization. (III)
  • Inpatient clinicians should ensure that the details of hospitalization, including the discharge medications and plans, are sent in a timely fashion to outpatient clinicians. (III)

Communication among practitioners is essential when patients move between primary care clinicians and other healthcare settings. When patients are referred to the emergency room, communication with the emergency room physician, both by phone and by transmission of essential data, such as pertinent medical conditions, the medication list, the patient’s most recent CD4 count and viral load, and any other pertinent clinical data, can improve the patient’s care and help prevent unnecessary testing or hospitalization. If the patient needs to be hospitalized and the primary care clinician is not the admitting physician, communication of these data to the admitting physician is essential.

Communication is essential between outpatient practitioners and all professionals involved in the patient’s care. This includes both nursing services and other consultants and ancillary providers such as physical therapists.

Appropriate Use of Chronic Care Services

RECOMMENDATION

Home Health Care

  • Home health nurses should be provided with a copy of the patient’s medication list and information regarding current medical conditions and mental health or substance use disorders. (III)

End of Life Care

  • Clinicians should encourage patients to prepare an advanced directive and designate a healthcare proxy and should review these arrangements at least annually.
  • As HIV disease progresses, clinicians should discuss patients’ feelings about end-of-life care before they are unable to make decisions. Any medical decisions that are made should be in conjunction with the patient, or, if the patient is unable to decide for neurologic reasons, with the patient’s healthcare proxy. (III)
  • Clinicians should be familiar with hospice services available in their area and should make referrals to them early enough for the patient to receive the full benefit of their support (III). Clinicians should work in conjunction with hospice staff to establish which medical interventions may still be appropriate as quality of life evolves or changes. (III)

AIDS adult day health care programs: AIDS Adult Day Health Care Programs (ADHCs) are designed to assist in meeting the healthcare needs of patients with HIV/AIDS who require a greater range of comprehensive healthcare services than can be provided in any single ambulatory setting but who do not require the level of services provided in a hospital or skilled nursing facility. Through a therapeutic environment, ADHCs are intended to improve and stabilize the health of patients with HIV/AIDS, assist patients with adherence support, reduce hospital stays, eliminate unnecessary visits to primary care clinicians and emergency rooms, and provide interventions in the form of one-on-one counseling and structured group activities for substance use and mental health disorders. Nursing care, nutritional services, case management, and HIV risk reduction, as well as auricular acupuncture and therapeutic massage, are also provided. For more information on these programs, contact 1-518-474-8162.

Home health care: Home care, including infusion therapy, can help maintain the patient’s health and reduce the need for hospitalization. AIDS Home Care Programs (AHCPs) ensure patients’ access to enhanced physician services, dental care, HIV prevention and education services, substance use and treatment services, pastoral care, mental health services, peer support, HIV clinical trials, and HIV therapies. AHCP services may be provided by a long-term home healthcare program or a Designated AIDS Center specifically authorized to provide these services.

AHCPs are responsible for arranging and/or providing the following: nursing services, home health aide services, medical supplies, equipment and appliances, physical and occupational therapy, speech pathology, nutritional services, medical social services, personal care services, and housekeeping services. Long-term home healthcare programs may also provide personal emergency response, meals on wheels, housing improvement, home maintenance, moving assistance, social daycare, and social transportation services.

End-of-life care: End-stage HIV infection often involves a series of treatments for opportunistic infections, tumors, or other life-threatening comorbid conditions, such as liver failure. When both the patient and the clinician agree that aggressive care is no longer desired or likely to succeed, supportive care with a goal to maximize comfort is appropriate.

Clinicians should work with hospice staff to establish which interventions may still be appropriate as quality of life declines. For example, continuing aggressive care of cytomegalovirus retinitis to prevent blindness is a treatment that may need to be continued even though the patient has elected to discontinue other active medications.

All Recommendations

Medical Care Criteria Committee

ALL RECOMMENDATIONS: PRIMARY CARE APPROACH
Introduction (April 2011)
  • Primary care clinicians should be capable of evaluating HIV-infected patients at all stages of HIV infection and should consult with a clinician who has experience with management of antiretroviral therapy (ART) according to current guidelines (see Antiretroviral Therapy). (III)
  • Clinicians should involve patients in decisions regarding HIV treatment. (III)
History and Ongoing Assessments (November 2014)
  • Clinicians should obtain a baseline and an ongoing HIV-related history according to Table 1: Comprehensive History and Ongoing Assessments for HIV-Infected Patients. (AI)
  • When obtaining an HIV-related history, clinicians should:
    • Use vocabulary that patients can understand, regardless of educational level (AIII)
    • Assess patients’ health literacy (AIII)
    • Determine the language in which the patient wishes to communicate and use a professional interpreter or sign language services when language or hearing barriers exist (AIII)
  • Clinicians should stress the confidential nature of discussions regarding sexual history, mental health, and substance use. (AIII)
  • Clinicians should address the importance of partner notification with HIV-infected patients. HIV and STI testing for partners, including testing for viral hepatitis, should be available onsite (for more information about partner notification, see www.health.ny.gov/diseases/aids/regulations/partner_services/index.htm).
  • All HIV-infected patients should receive baseline and ongoing assessment for the following (AI):
    • Mental health disorders
      • Depression (every visit)
      • Anxiety (at least annually)
      • Post-traumatic stress disorder (at least annually)
    • Cognitive function (at least annually)
    • Sleep habits and appetite assessment (every visit)
    • Alcohol and substance use (at least annually; at-risk drug and alcohol users should be screened more frequently to identify escalation of present levels of use or harmful consequences from use.)
    • Suicidal/violent ideation (every visit)
    • Psychosocial status, including domestic violence, family and social support, and housing status (at least annually)
  • Clinicians should use selected brief screening instruments when performing the mental health and substance use assessment. The chosen screening instruments should be tailored for optimal use at initial, annual, and interim visits and adjusted for the patient’s mental health or substance use history (see Mental Health Screening Tools. (AIII)
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (AII)
Comprehensive Physical Exam (November 2014)
  • Clinicians should perform a baseline and annual comprehensive physical examination for all HIV-infected patients. All standard elements of a comprehensive physical examination should be performed, with particular attention to areas potentially affected by HIV.
  • Clinicians should note abnormalities and changes in general appearance, body habitus, physical well-being, frailty, and mobility.
  • Clinicians should assess vital signs, weight, and body mass index (BMI) at each visit.
  • Clinicians should:
    • Ask HIV-infected patients about pain at each visit
    • Use a validated pain scale to track pain over time
    • Document the severity and location of pain and precipitating factors
    • Attempt to identify underlying causes of pain and respond with efforts to alleviate it
    • Provide referral to a pain-management specialist when the patient’s symptoms do not respond to treatment in the primary care setting
  • Clinicians should not deny treatment of pain because of a patient’s past or current history of addiction; clinically appropriate pain management in substance users requires careful individualized judgment.
  • Clinicians should assess patients with chronic pain for fatigue and mental health disorders.
  • Patients with CD4 counts <50 cells/mm3 should be examined by an ophthalmologist at baseline and every 6 months. (AIII)
  • Patients with visual disturbances or unremitting ocular symptoms, regardless of CD4 cell count, should be evaluated by an ophthalmologist. (AIII)
  • Asymptomatic patients without a significant history of eye conditions who have CD4 cell counts ≥50 cells/mm3 should receive retinal examinations according to the standard schedule for all adults.
  • Clinicians should ascertain whether HIV-infected patients have a regular oral health provider and should refer:
    • Dentulous patients for hygiene and intraoral examinations every 6 months, including screening for dental caries, gum disease, and oral cancer (AIII)
    • Edentulous patients for intraoral examinations annually, including assessment for denture fit and screening for mucosal lesions including oral cancer (AIII)
  • All referrals should be documented in the patient’s medical record.
  • As part of the annual physical examination, clinicians should inspect the patient’s oral cavity.
  • Clinicians should examine all HIV-infected patients for anogenital ulcerative lesions.
  • Clinicians should perform a gynecologic examination in all HIV-infected women or refer them to a gynecologist at baseline and at least annually.
  • At baseline and as part of the annual physical examination for all HIV-infected adults, regardless of age, clinicians should:
    • Inquire about rectal symptoms, such as itching, bleeding, discharge, diarrhea, or pain
    • Perform a visual inspection of the perianal region
    • Perform a digital rectal examination
  • Clinicians should refer any patient with abnormal anal physical findings, such as warts, hypopigmented or hyperpigmented plaques/lesions, lesions that bleed, or any other lesions of uncertain etiology, for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
  • Transgender patients should receive a genitourinary examination according to standards of care for their anatomy. Male-to-female transgender patients with a neo-vagina should receive pelvic examinations according to HIV care guidelines for natal females. Before performing a pelvic examination, the clinician should explain the medical reasons for the examination. (AIII)
  • As part of the routine mental health assessment for HIV-infected patients, clinicians should assess cognitive function.
  • Clinicians should assess gait, cranial nerves, reflexes, and balance in HIV-infected patients, as well as examine for sensory, vibratory, motor, and cerebellar abnormalities.
  • Clinicians should refer HIV-infected patients with more complex suspected or proven peripheral neuropathy syndromes to a neurologist to assist with the diagnosis and management.
Labs and Diagnostic Testing (March 2011)
  • Clinicians should order appropriate laboratory assessments and screening tests for management of HIV-infected patients (see Table 3). (III)
  • Clinicians should use an assay with a high upper limit of detection (e.g., ≥750,000 copies/mL) for initial measurement of HIV viral load in ART-naïve patients. (III)
  • Clinicians should obtain viral load before vaccinations and not during intercurrent illness because these situations may lead to a transient elevation in viral load. (III)
  • Clinicians should perform resistance testing under the following circumstances:
    • At baseline, regardless of whether ART is being initiated (genotypic testing)
    • In ART-naïve patients before initiation of ART (genotypic testing)
    • In patients experiencing treatment failure or incomplete viral suppression while receiving ART (genotypic and/or phenotypic testing)
  • Clinicians should seek expert consultation for interpretation of genotypes. (III)
  • The CD4 lymphocyte profile should include both the absolute count and percentage. (I)
  • Clinicians should obtain a TST (tuberculin skin test, commonly known as PPD) or other FDA-approved test for diagnosis of latent tuberculosis infection, unless the patient has previously tested positive or has had previously documented TB. (I)
  • After active tuberculosis has been excluded, clinicians should prescribe TB prophylaxis when a TST results in induration of ≥5 mm or when another FDA-approved test indicates the presence of latent TB infection. (I)
  • Clinicians should screen HIV-infected patients for syphilis by obtaining a non-treponemal test (RPR or VDRL) with verification of reactive test by confirmatory fluorescent treponemal antibody absorbance (FTA-Abs) or treponema pallidum particle agglutination (TP-PA) tests at baseline and at least annually. Patients with continued high-risk behavior should be screened for syphilis every 3 months.
  • Clinicians should screen sexually active HIV-infected women under the age of 25 for gonorrhea and chlamydia at baseline and at least annually. Clinicians should screen all sites of possible exposure, including the cervix, rectum, and pharynx. Culture or nucleic acid amplification tests (NAT) should be used to screen for gonorrhea. Immunofluorescence or DNA amplification should be used for chlamydia.
  • Clinicians should screen women 25 years of age or older for gonorrhea and chlamydia at baseline and at least annually if they have or have had a recent sexually transmitted infection, have multiple sexual partners, have had a new sexual partner, or have a sexual partner with symptoms of an STI.
  • Clinicians should screen all HIV-infected men with ongoing high-risk sexual behaviors for gonorrhea and chlamydia at baseline and at least annually. Clinicians should screen all sites of possible exposure, including the urethra, rectum, and pharynx.
  • Clinicians must report all suspected or confirmed syphilis, chancroid, gonococcal, and chlamydial infections to the local health department of the area where the patient resides according to NYS requirements (also see Communicable Disease Reporting Requirements).
  • Clinicians should obtain cervical Pap tests for all HIV-infected women at baseline, 6 months after baseline, and then repeat annually, as long as results are normal.
  • Colposcopy should be performed for women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis.
  • Clinicians should repeat abnormal Pap tests every 3 to 6 months thereafter until there have been two successive normal cervical Pap tests. Women with cervical HSIL also should be referred for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
  • Clinicians should obtain at least an annual Pap test in HIV-infected women who have undergone either a supracervical or total hysterectomy.
  • Clinicians should obtain anal cytology at baseline and annually in the following HIV-infected populations:
    • Men who have sex with men
    • Any patient with a history of anogenital condylomas
    • Women with abnormal cervical/vulvar histology
  • Clinicians should refer patients with abnormal anal cytology for high-resolution anoscopy and/or examination with biopsy of abnormal tissue. (III)
Health Promotion and Behavioral Counseling (March 2007)
  • Clinicians should provide routine HIV risk-reduction counseling and behavioral health counseling for HIV-infected patients. (I)
  • Clinicians should discuss safer sexual practices with HIV-infected patients on a routine and ongoing basis. (I)
  • Clinicians should routinely discuss with patients the importance of disclosure to partners. Patients should be educated about the options for voluntary partner notification. These discussions should be clearly documented. Information about HIV reporting and partner notification in New York State is available at Provider Reporting & Partner Services. (I)
  • Clinicians should emphasize that transmission of HIV may occur during unprotected sex, even when patients have undetectable HIV plasma viral loads. (I)
  • Clinicians should recommend the correct and consistent use of latex or, when latex allergies exist, polyurethane male condoms and should discuss the option of using polyurethane female condoms. (I)
  • Clinicians should instruct patients in the proper use of condoms, dental dams, and other barriers to reduce the risk of HIV transmission. (I)
  • Clinicians should educate their patients to avoid using condoms and creams containing nonoxynol-9. (I)
  • When current alcohol or other substance use is identified, clinicians should discuss the possible effects of such use on the patient’s general health and HIV medications, as well as options for treatment if indicated. These discussions should be properly documented in the patient’s chart. (I)
  • Clinicians should evaluate for possible interactions among illicit drugs and prescription drugs. (I)
  • Clinicians should issue prescriptions for new needles and syringes to patients who inject drugs.
  • Clinicians should discuss with patients other options for accessing new needles and syringes, including use of the Expanded Syringe Access Program and Syringe Exchange Programs, New York State’s two syringe access initiatives. (I)
  • Clinicians should collaborate with social work staff and other mental health providers, when available, to determine which treatment programs or substance use services best meet the patient’s needs. (I)
  • Clinicians should assess smoking status and should encourage those who smoke to stop (I). Pharmacotherapy and referrals to smoking cessation programs should be provided if the patient is interested.
  • Clinicians should discuss family planning with patients, including risks to the mother and fetus during pregnancy.
  • Clinicians or a member of the healthcare team should screen all male and female HIV-infected patients for current and lifetime domestic violence at baseline and annually. (I)
  • Prior to screening patients for domestic violence, clinicians should discuss confidentiality and exceptions to confidentiality, including instances of suspected child abuse and maltreatment and intent to harm self or others.
  • Domestic violence screening should be performed only when the patient is alone.
  • The clinician or a member of the healthcare team should perform a psychosocial assessment of HIV-infected patients, including housing status, at baseline and at least annually. (I)
  • The clinician should work with the patient’s case manager to provide necessary medical guidance related to psychosocial issues that are potential barriers to treatment adherence. (I)
Preventive Medicine (March 2011)
  • Clinicians should discuss general preventive healthcare and health maintenance with all HIV-infected patients routinely and, at a minimum, annually. (I)
  • Clinicians should perform standardized age- and sex-appropriate health-maintenance interventions, such as cancer screening, in HIV-infected patients according to the same guidelines used for non-HIV-infected patients (see text). (I)
  • Clinicians should instruct patients on how to perform breast and testicular self-examinations. (III)
  • Clinicians should initiate prophylaxis for specific opportunistic infections as indicated in Table 4: Initiation of Primary OI Prophylaxis and discontinue it as indicated in Table 5: Discontinuation of OI Prophylaxis. (I)
Coordination of Care (March 2007)
  • As part of the initial visit, the clinician or other member of the healthcare team should educate new patients about the following items (III):
    • How to access emergency services (provide a phone number for 24-hour services)
    • Whom to contact to schedule appointments
    • How to obtain laboratory and radiology results, medical records, and other reports
  • After receiving patient consent, clinicians should share information with other agencies from which their patients are receiving services. (III)
  • Case management should be used to enhance coordination of care provided by agencies such as home care, nutrition services, and nursing services and to prevent duplication of services. (III)
  • Clinicians should regularly involve case managers in case conferences to discuss psychosocial issues that may affect a patient’s ability to adhere to care. (III)
Appropriate Use of Acute Care Services 
  • Outpatient clinicians who do not provide inpatient care should have a network of practitioners with whom they can communicate easily should their patients require hospitalization. (III)
  • Inpatient clinicians should ensure that the details of hospitalization, including the discharge medications and plans, are sent in a timely fashion to outpatient clinicians. (III)
Appropriate Use of Chronic Care Services 
  • Home health nurses should be provided with a copy of the patient’s medication list and information regarding current medical conditions and mental health or substance use disorders. (III)
  • Clinicians should encourage patients to prepare an advanced directive and designate a healthcare proxy and should review these arrangements at least annually.
  • As HIV disease progresses, clinicians should discuss patients’ feelings about end-of-life care before they are unable to make decisions. Any medical decisions that are made should be in conjunction with the patient, or, if the patient is unable to decide for neurologic reasons, with the patient’s healthcare proxy. (III)
  • Clinicians should be familiar with hospice services available in their area and should make referrals to them early enough for the patient to receive the full benefit of their support (III). Clinicians should work in conjunction with hospice staff to establish which medical interventions may still be appropriate as quality of life evolves or changes. (III)

Preventive Care and Screening Guidelines

Anal Dysplasia and Cancer Guideline

Cervical Dysplasia and Cancer Guideline

Gynecological Care

Women with HIV Infection Guidelines Committee, February 2009

RECOMMENDATIONS
  • Clinicians should obtain a baseline gynecological history for HIV-infected women (see text).
  • Clinicians should perform a gynecological examination in women or refer them to a gynecologist at baseline and at least annually.
  • Clinicians should consider social, cultural, religious, or behavioral issues that may affect a woman’s willingness to undergo a complete pelvic examination, such as previous history of sexual assault, partial or complete female circumcision, genital mutilation, or infibulation.

Primary care clinicians should address women’s health issues in the provision of routine HIV care. In addition to a comprehensive gynecological history and examination, clinicians should provide sexual risk-reduction counseling for all HIV-infected women.

Strategies that may help alleviate a woman’s concerns about undergoing a pelvic examination include the following: addressing the patient’s fears, explaining each step of the examination prior to performing it, using a smaller speculum, and/or postponing the pelvic examination until the patient becomes more acquainted with the clinician. Also, some women may prefer to be examined by a female clinician.

History

Elements of a gynecological history for HIV-infected women include the following:

  • Age of menarche
  • Menstrual history: frequency, duration, last menstrual period
  • Number of pregnancies and outcomes: full-term and premature births, miscarriages, terminations
  • Date of last Pap test and results
  • History of abnormal Pap tests
  • History of GYN procedures: LEEP, ablation, cone biopsy, hysterectomy, tubal ligation
  • History of STIs, bacterial vaginosis, multiple or difficult to treat vaginal yeast infections
  • Contraceptive use and needs
  • Genitourinary symptoms: vaginal discharge, vaginal pain, dysuria, genital/rectal warts or ulcers, bleeding

Physical Exam

Elements of a gynecological physical examination for HIV-infected women include the following:

Breast: Examine for: Masses, nipple discharge, dimpling, enlargement. Refer women ≥40 for annual mammogram.

Pelvis: Examine for friable cervix, venereal warts (HPV), vaginal discharge, classic and atypical herpes simplex virus (HSV), ulcerative genital disease, cervical motion tenderness, lesions on the vulva or perineum

Perianal: Examine for visible anal lesions (particularly HSV and/or HPV), evidence of skin abnormality around the anus (Candida), hemorrhoids. Perform digital rectal examination (baseline and annually). Refer women with abnormal anal physical findings for high-resolution anoscopy and/or examination with biopsy

Cervical cytology: Obtain cervical Pap test at baseline, 6 months after baseline, then annually as long as results are normal.

  • Abnormal results should be repeated every 3 to 6 months until two successive normal Pap tests are reported
  • Perform colposcopy for women with abnormal Pap test results; follow-up varies on a case-by-case basis
  • Refer women with cervical HSIL for high-resolution anoscopy and/or examination with biopsy
  • Anal Cytology:
  • Obtain anal Pap test for women with a history of anogenital condyloma or abnormal cervical/vulvar histology (baseline and annually)
  • Refer women with abnormal anal cytology for high-resolution anoscopy and possible biopsy

Syphilis screening:* RPR or VDRL with verification of reactive tests by confirmatory FTA-Abs or TP-PA (baseline and at least annually). Screen patients with continued high-risk behavior every 3 months.

Gonorrhea and chlamydia screening:*Screen all sites of exposure, including the cervix, rectum, and pharynx, as follows:

  • Sexually active women under the age of 25 at baseline and at least annually
  • Women 25 years of age or older if they have or have had a recent STI, have multiple sexual partners, have had a new sexual partner, or have a sexual partner with symptoms of an STI (baseline and at least annually)
  • Screen for gonorrhea using culture or nucleic acid amplification tests (NAT)
  • Screen for chlamydia using immunofluorescence or DNA amplification

*Patients who continue to engage in unsafe sexual practices are at increased risk for STIs. More frequent screening may be indicated for patients at higher risk.

Insomnia Screening and Treatment (Quick Reference Guide)

Mental Health Guidelines Committee, April 2013

Download PDF
Download PDF

Insomnia occurs frequently in HIV-infected patients and during all stages of HIV disease [1]. Although insomnia is not unique to the HIV-infected population, insomnia screening should be part of routine HIV care due to the potentially negative effects of insomnia on health, including HIV disease progression.

What is insomnia? Difficulty falling asleep; frequent awakenings during sleep; early morning awakening; or non-restorative sleep despite adequate sleep duration

Possible causes: 1) Major life events, such as the death of a loved one; 2) Changes in sleeping environment (e.g., when in the hospital); 3) Physical and mental health disorders; 4) Prescription or OTC medication use; 5) Use or relapse of use of alcohol or other substances [2-4]

Possible consequences of insomnia: Fatigue, irritability, elevated blood pressure, excessive daytime sleepiness; non-adherence to ART [5]; increase in pain symptoms and worsening of physical health conditions [6]; relapse of psychiatric symptoms (e.g., anxiety, depression, mania).

RECOMMENDATIONS
  • Clinicians should ask patients at routine monitoring visits about sleep quality and difficulty initiating or maintaining sleep.
  • When an HIV-infected patient reports insomnia, primary care clinicians should:
    • Assess the patient’s sleep patterns, as well as perform a differential diagnosis, to clarify the nature of the patient’s insomnia
    • Exclude and manage causes of secondary insomnia
    • When possible, refer the patient at least once for evaluation by a psychiatrist or clinical psychologist
    • Discuss sleep hygiene with the patient and consider nonpharmacologic approaches for treating insomnia before prescribing medications
Click to enlarge
Click to enlarge

Sleep assessment evaluation checklist for clinicians: Suggest the patient keep a sleep log, which could include the following:

  • Events prior to bedtime, including emotional stressors and the consumption of alcohol or caffeine-containing beverages
  • Time spent awake in bed before falling asleep
  • Number, time, and length of awakenings
  • Final time of morning awakening
  • Time spent awake in bed before rising
  • Frequency and duration of naps during the day
  • Patient or bed partner observations of snoring, interrupted breathing, abnormal leg movements

Differential Diagnosis

Substance use etiologies: Caffeine, nicotine, alcohol, illicit drug use (particularly stimulants) 

  • Alcohol may help induce sleep, but its use is associated with sleep disruptions)

Mental health etiologies (the most common contributor to insomnia is the presence of a mental health disorder [7]):

  • Depression and anxiety disorders
  • Severe psychiatric disorders, including mania and psychosis
  • Side effects of psychotropic medications, including selective seratonin-reuptake inhibitors (SSRIs)

Medical conditions:

  • Pain
  • Respiratory: dyspnea and sleep apnea
  • Gastrointestinal: gastroesophageal reflux
  • Endocrinologic: hyperthyroidism, menopause
  • Neurologic: cognitive impairment, neuropathy, periodic limb movements in sleep or restless limb syndrome
  • Cardiopulmonary: lung disease, congestive heart failure
  • Nephrologic/urologic: chronic kidney disease, frequent urination and incontinence

Medications:

  • ART medications (e.g., efavirenz, lamivudine)
  • β-blockers
  • Bronchodilators
  • Calcium channel blockers
  • Corticosteroids
  • Decongestants
  • Immunomodulators (e.g., interferons, interleukin-2)
  • Trimethoprim-sulfa
  • Dapsone
  • Amphotericin
  • Fluconazole
  • Isoniazid
  • Diuretics taken at bedtime

Sleep Hygiene Strategies

Encourage the following “To Do’s”:

  • Take warm baths before bed
  • Exercise for at least 30 min/day most days of the week
  • Maintain a bedtime routine (e.g., going to bed and waking up at a set time)
  • Make bedroom cool, dark, and quiet
  • Place the clock out of sight
  • If unable to fall asleep after 20 minutes, leave bed and do something relaxing (e.g., reading); return to bed later

Discourage the following “Don’ts”:

  • Consuming caffeine (coffee, tea, chocolate, soda), alcohol, or nicotine before bedtime
  • Eating a large meal just before bedtime
  • Napping during the day
  • Exercising within 2 hours of bedtime
  • Working, eating, reading, or watching television in bed. 

Cognitive behavioral strategies: Referral to a sleep specialist to assist patients with cognitive-behavioral techniques may benefit some individuals with insomnia. Techniques include: cognitive therapy, relaxation training, sleep restriction, and phototherapy.

Pharmacologic strategies: 

  • Assess for patient use of OTC agents for insomnia and offer to prescribe an FDA-approved agent as a better option (e.g., offer ramelteon instead of OTC melatonin)
  • Avoid prescribing medications for sleep disturbance that have narrow therapeutic ranges and potential for abuse (e.g., barbiturates, choral hydrate, and meprobamate)
  • Limit to 1 week the use of antihistamines for promoting sleep in order to avoid worsening of symptoms due to long-term use
  • Advise patients of the potential side effects of melatonin-agonist therapy, including OTC preparations, particularly severe hypersensitivity reactions
  • Do not prescribe tricyclic antidepressants to patients with cardiac conduction problems; although some clinicians prescribe these agents for insomnia, most are not FDA-approved for this purpose

Checklist of questions when selecting a pharmacologic agent for insomnia:

  • Will this agent improve symptoms that may be contributing to the patient’s insomnia (e.g., depression, anxiety, neuropathic pain, etc.)?
  • Will this agent pose risks to the patient based on comorbid medical conditions?
  • Will this agent pose risks based on interactions with other medications, (e.g., zolpidem, zaleplon, and eszopiclone should be used with caution in patients taking protease inhibitors)?
  • Is this the optimal agent for a patient with a current or pasthistory of alcohol or sedative abuse/dependence?
  • Can the patient afford the prescribed medication?

Agents with an FDA-approved indication for insomnia:

  • Antihistamines: Diphenhydramine, doxylamine, hydroxyzine
  • Non-benzodiazepine hypnotics: Zolpidem, zolpidem-CR, zaleplon, eszopiclone
  • Melatonin agonist: Ramelteon
  • Antidepressants: Trazodone, doxepin
  • Benzodiazepine hypnotics: Flurazepam, quazepam, estazolam, triazolam, temazepam, lorazepam
References:
  1. Reid S, et al. Psychosom Med 2005;67:260-269.
  2. Feige B, et al. Alcohol Clin Exp Res 2007;31:19-27.
  3. Brower KJ. Sleep Med Rev 2003;7:523–539.
  4. Mahfoud Y, et al. Psychiatry 2009;6:38-42.
  5. Ammassari A, et al. J Acquir Immune Defic Syndr 2001;28:445-449.
  6. Ancoli-Israel S. Am J Manag Care 2006;12(8 Suppl):S221-S229.
  7. Reid S, et al. Psychosom Med 2005;67:260-269.

 

Meningococcal Disease (NYSDOH Health Advisories)

NYSDOH Meningococcal Vaccine Recommendations for HIV-Infected Individuals and Those at High Risk of HIV Infection

October 25, 2016 | Download the 10/25/16 NYS Health Advisory 

On June 22, 2016, the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) voted to recommend that persons aged ≥2 months with HIV infection should receive meningococcal conjugate (MenACWY) vaccine, either MenACWY-D (Menactra®), MenACWY-CRM (Menveo®) or, as age-appropriate, Hib-MenCY-TT (MenHibrix®, recommended for ages 2-18 months).

This recommendation was made based on epidemiologic data demonstrating an increased risk of invasive meningococcal disease (IMD) due to serogroups C, W, and Y among HIV-infected persons in the United States. HIV-infected individuals have suppressed immune responses to MenACWY vaccine, as well as waning of vaccine-induced immunity. For this reason, a multidose primary series and regular booster doses are necessary to maintain protection against IMD. HIV-infected persons have not been demonstrated to be at increased risk of serogroup B disease, and use of serogroup B (MenB) vaccine has not been studied in this group; for this reason MenB vaccine is not recommended for HIV-infected persons unless they have another indication for this vaccine.

In response to the ACIP recommendations, the NYSDOH advises healthcare providers to administer MenACWY vaccine to:

  • All HIV-infected children and adults aged 2 months or older, and
  • HIV-negative individuals at ongoing high risk for HIV infection, to include:
    • Men who have sex with men (MSM) who are candidates for HIV pre-exposure prophylaxis (PrEP) as described in the NYSDOH AIDS Institute “Guidance for the Use of Pre-Exposure Prophylaxis to Prevent HIV Transmission” and
    • Transgender individuals who are candidates for PrEP.

Read the full NYS Health Advisory, which includes additional information regarding dosing and vaccine cost reimbursement.

See also: CDC Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons—Advisory Committee on Immunization Practices, 2016.

Previous IMD-Related Health Advisories and Alerts

More Information

Menstrual Disorders Guideline

Smoking Cessation Guideline

See Smoking Cessation in HIV-Infected Patients in the Substance Use guidelines.

Coinfections and Complications Guidelines

Gastrointestinal Complications Guideline

HAV-HIV Coinfection Guideline

HBV-HIV Coinfection Guideline

HCV-HIV Coinfection Guideline

January 2017

The Medical Care Criteria Committee of the New York State Department of Health (NYSDOH) AIDS Institute recommends that all HIV/HCV co-infected patients be considered candidates for hepatitis C treatment, regardless of fibrosis stage.

The NYSDOH AIDS Institute guideline on HIV-HCV coinfection is currently under revision, with expected publication in early 2017. For up-to-date information on hepatitic C treatment, see IDSA-AASLD Recommendations for Testing, Managing, and Treating Hepatitis C.

 

Kidney Disease Guideline

Oral Health Complications

Oral health care is a critical component of comprehensive HIV medical management. Development of oral pathology is frequently associated with an underlying progression of HIV-disease status. A thorough soft-tissue examination may reveal pathology associated with dysphagia or odynophagia. Dental problems can result in or exacerbate nutritional problems. In addition, psychosocial and quality-of-life issues frequently are associated with the condition of the oral cavity and the dentition.

RECOMMENDATIONS
  • Primary health care providers should make an initial dental referral for every patient under their care. Oral health care providers should examine all patients on a semiannual basis for dental prophylaxis and other appropriate preventive care.
  • The primary health care provider should examine visually and through palpation the patient’s lips, labial and buccal mucosa, all surfaces of the tongue and palate, and the floor of the mouth. The gingiva should be examined for signs of erythema, ulceration, or recession.
  • Patients presenting with oral mucosal, gingival, or dental lesions should be referred promptly to an oral health care provider for appropriate diagnostic evaluation and treatment.
  • Health care providers should instruct patients in preventive oral health care, including dental visits, brushing, flossing, and the use of fluorides and antimicrobial rinses.
  • In the later stages of HIV disease, greater numbers of oral lesions and aggressive perio-dontal breakdown are more likely; therefore, oral health care visits should be scheduled more frequently.

Medications and oral health: Many of the medications received by HIV-infected patients have side effects that may manifest in the oral cavity. Potential side effects include the following:

  • Candidal growth: Antibiotics may cause or exacerbate
  • Xerostomia: Antihistamines, antidepressants, antipsychotics, antihypertensives, and anticholinergic agents
  • Increased risk of dental caries: Clotrimazole troches and nystatin suspension pastilles (contain sugar)
  • Gingival hyperplasia: Phenytoin
  • Oral ulcers: Zalcitabine (DDC)

Clinical Manifestations and Management of HIV-Related Periodontal Disease Guideline

Committee Members and External Reviewers

Clinical Manifestations of HIV-Related Periodontal Disease

January 2017

Leadership

  • Chair: Stephen N. Abel, DDS, MSD, University at Buffalo-SUNY, Buffalo, NY
  • Deputy Medical Director: Lyn C. Stevens, MS, NP, ACRN, Albany, NY, New York State Department of Health AIDS Institute, Office of the Medical Director

Contributing Members

  • Victor M. Badner, DMD, MPH, North Bronx Healthcare Network, Bronx, NY
  • Mary Therese Biltucci, RDH, MA, University of Rochester, Rochester, NY
  • Stanley J. Boyd, DMD, Healthy Chelsea Dentistry, New York, NY
  • Gwen Cohen Brown, DDS, FAAOMP, New York City College of Technology, Brooklyn, NY
  • Dolores Cottrell-Carson, DDS, MSHA, New York State Board for Dentistry, Albany, NY
  • Maria de los Angeles Figueroa, DMD, Bronx-Lebanon Hospital Center, Bronx, NY
  • Mary J. D’Silva, DDS, NYS DOC and Community Supervision, Albany, NY
  • Robert D. Kelsch, DMD, Northwell Health, Manhasset, NY
  • Michael A. Kozlowski, DDS, Unity Dental Group, Rochester, NY
  • Kareem J. Merrick, DDS, Harlem United Community Clinic, New York, NY
  • Calix Ramos-Rodriguez, DMD, Lutheran Medical Center, Brooklyn, NY
  • Miriam R. Robbins, DDS, MS, Winthrop University Hospital, Mineola, NY
  • Dara J. Rosenberg, DDS, MS, MPH, St. Barnabas Hospital, Bronx, NY
  • Terrence T. Thines, DDS, MS, SUNY Upstate Medical University, Syracuse, NY

Agency, Consumer, and Program Liaisons

  • Consumer Liaisons: Jahlove Serrano, Bronx, NY; David Martin, New York, NY, New York State Department of Health AIDS Institute Consumer Advisory Committee
  • New York State Department of Corrections and Community Supervision: Britta Viereckl-Prast, DMD, Bedford Hills,  New York

External Contributors and Peer Reviewers

  • Abrahim Maddi, DDS, MSc, PhD, Unifersity at Buffalo, Buffalo, NY
  • John T. Grbic, DMD, MMSc, Columbia University Medical Center, New York, NY
  • Mark I. Ryder, DMD, University of California San Francisco School of Dentistry, San Francisco, CA

Perioperative Management Guideline

Risks

Medical Care Criteria Committee, January 2012

Risk to Patients

Effective antiretroviral therapy (ART) for people living with HIV has resulted in a life expectancy that approaches that of the general population [1]. Both urgent and elective surgical procedures are a common part of HIV medical care. Although the relative risk of surgery in HIV-infected patients has been debated in the literature, retrospective studies have indicated favorable outcomes despite HIV serostatus and regardless of extent or duration of surgery [2-4]. 

Overall health, particularly the presence or absence of organ failure, and nutritional state (albumin <2.5g/dL) have been found to be more reliable predictors of surgical outcome than CD4 count or viral load in HIV-infected patients [5-8]. Some studies have shown poorer surgical outcomes for individuals with low CD4 counts, although this has not been a consistent finding [9,10]. Viral suppression also has not been conclusively shown to improve surgical outcomes; however, in the setting of elective surgery, it is still recommended that ART be optimized preoperatively (see Antiretroviral Therapy).

KEY POINT
  • Neither CD4 cell count nor HIV viral load should be used as sole determinants of a given patient’s surgical risk [5].

This chapter addresses the perioperative management of HIV-infected individuals undergoing necessary surgical procedures. Surgical risk assessment for HIV-infected individuals is highly individualized, and all aspects of the HIV-infected patient’s clinical profile, including the indication for surgery, should be evaluated and discussed with the patient [5].

Risk to the Surgical Team

RECOMMENDATION
  • Universal surgical precautions that apply to all patients should be followed. (AIII)

Data regarding HIV transmission risk through various types of non-surgical exposures suggest that risk to the surgical team is theoretically lower when patients have undetectable viral loads. However, universal surgical precautions that apply to all patients should be followed, regardless of an HIV-infected patient’s viral load.

References:
  1. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies. Lancet 2008;392:293-299. [PubMed]
  2. Guth AA, Hofstetter SR, Pachter HL. Human immunodeficiency virus and the trauma patient: Factors influencing post operative infectious complications. J Trauma 1996;41:251-255. [PubMed]
  3. Sewell CA, Derr R, Anderson J. Operative complications in HIV-infected women undergoing gynecologic surgery. J Reprod Med 2001;46:199-204. [PubMed]
  4. Jones S, Schechter CB, Smith C, et al. Is HIV infection a risk factor for complications of surgery? Mt Sinai J Med 2002;69:329-333. [PubMed]
  5. Madiba TE, Muckart DJJ, Thomson SR. Human immunodeficiency disease: How should it affect surgical decision-making? World J Surg2009;33:899-909. [PubMed]
  6. Bizer L, Pettorino R, Ashikari A. Emergency abdominal operations in the patient with acquired immunodeficiency syndrome. J Am Coll Surg1995;180:205-209. [PubMed]
  7. Yii MK, Saunder A, Scott DF. Abdominal surgery in HIV/AIDS patients: Indications, operative management, pathology and outcome. Aust N Z J Surg1995;65:320-326. [PubMed]
  8. Harris HW, Schecter WP. Surgical risk assessment and management in patients with HIV disease. Gastroenterol Clin North Am 1997;26:377-391. [PubMed]
  9. Čačala SR, Mafana E, Thomson SR, et al. Prevalence of HIV status and CD4 counts in a surgical cohort: Their relationship to clinical outcome. Ann R Coll Surg Engl 2006;88:46-51. [PubMed]
  10. Guild GN, Moore TJ, Barnes W, et al. CD4 count is associated with postoperative infection in patients with orthopaedic trauma who are HIV positive.Clin Orthop Relat Res 2011 Dec 30. Epub ahead of print. [PubMed]

Preoperative Evaluation

January 2012

RECOMMENDATIONS
  • The preoperative evaluation of HIV-infected patients should be the same as that for non-HIV-infected patients; however, clinicians should carefully assess for the following conditions that are more prevalent in the HIV-infected population (AIII):
    • hepatic and renal dysfunction
    • coronary artery disease and cardiac risk
    • coagulopathy, thrombocytopenia, and neutropenia
    • active alcohol or substance use, including both prescription and non-prescription drug use
    • history of prior infection/colonization with methicillin-resistant Staphylococcus aureus (MRSA), particularly in men who have sex with men (MSM)
    • drug allergies
  • Clinicians should obtain urine toxicology, with patient consent, if the substance use history is unreliable and there are concerns about substance use. Elective surgery should be deferred until active substance use has been addressed. (AIII)
  • Individuals with a history of MRSA colonization or infection should receive vancomycin instead of cefazolin for prophylaxis when indicated. (AIII)

Preoperative evaluation of the HIV-infected patient is similar to that of the general population; however, comorbidities, active substance use, and MRSA may be more prevalent in the HIV-infected population (see Table 1).

Table 1: Surgical Management Considerations for HIV-Infected Patients with Comorbidities and Other Conditions
Comorbidity Risks Pre- and Perioperative Recommendations Comments

Hepatic dysfunction: Increased prevalence of hepatic dysfunction from ART or from preexisting liver disease.

Surgical risk: Co-infection with HBV or HCV may predispose to increased bleeding risk due to coagulopathy or thrombocytopenia.

  • Assess for hepatic dysfunction preoperatively because of the possible impact on dosing or selection of anesthetics, perioperative antibiotics, and other medications.
Renal dysfunction: Increased prevalence of renal dysfunction from HIV-associated nephropathy (HIVAN) and other causes [1].
  • Assess for renal dysfunction preoperatively because of the possible impact on dosing or selection of anesthetics, perioperative antibiotics, and other medications.
  • If there are renal function changes in the perioperative period, review ART regimen for agents that may require renal dose adjustment.

Coronary artery disease and cardiac abnormalities: Increased prevalence of CAD from metabolic dysfunction due to HIV infection and/or ART [2-4].

QT prolongation or other cardiac abnormalities may occur in advanced HIV infection or in patients receiving certain medications [a].

  • Assess for coronary artery disease preoperatively.
  • Perform careful review of preoperative EKG results.
  • Anti-arrhythmics, methadone, PIs, antipsychotics, or macrolide antibiotics can cause QT prolongation or other cardiac abnormalities, especially if more than one such agent is administered concurrently.

Respiratory complications: Prevalence of underlying pulmonary disease is increased due to the increased risk for bacterial pneumonia [5,6] and high prevalence of smoking [7,8] in HIV-infected patients.

Surgical risk: Risk for postoperative pneumonia is increased in HIV-infected patients.

  • Carefully evaluate for respiratory complications in the perioperative period.

Thrombocytopenia and neutropenia: Idiopathic thrombocytopenic purpura may occur at any stage of HIV infection.

Neutropenia is common in HIV-infected individuals with severe immunosuppression [b].

  • Consult with hematologist prior to surgical procedure when platelet counts approach 50,000 per µl.
  • Routine use of G-CSF not recommended [9] but in perioperative period may consider G-CSF [c] use to maintain absolute neutrophil count >1,000 cells/mm3 (CIII) [10,11].
  • Neutropenia may be caused by medications (e.g., ZDV, TMP-SMX), HIV infection itself, bone marrow infiltration from malignancy or systemic infection.
  • G-CSF is recommended over GM-CSF due to theoretical concerns regarding potential stimulation of HIV replication by the latter, although the possible mechanism by which GM-CSF might affect HIV-1 replication remains unclear [10].
Hemophilia
  • Coordination between surgical team and hematologist is recommended for transfusion of factor replacement in anticipation of surgery.

Substance use (SU): SU disorders are more prevalent in HIV-infected individuals than in the general population [12,13].

Surgical risks: Increased risk for complications from surgery and anesthesia, notably cardiac complications associated with cocaine use; increased risk for withdrawal symptoms in the postoperative period for unrecognized alcohol, benzodiazepine, or heroin use [d].

  • Obtain detailed history of substance use.
  • Consider obtaining urine toxicology screen, with patient consent.
  • For elective surgery, observe appropriate period of abstinence with the use of substitute medications such as methadone or benzodiazepines as appropriate.
  • Alcohol withdrawal may be life-threatening if symptoms are not recognized early.
Methicillin resistant staphylococcus aureus (MRSA): Community-acquired MRSA infection is more common in MSM than in the general population [14].
  • Assess for a history of previous MRSA infection/colonization, particularly in MSMs.
  • Use vancomycin instead of cefazolin for prophylaxis when indicated in patients with positive history of MRSA.
Drug allergies: HIV-infection is associated with a higher incidence of medication allergies.
  • Obtain a careful history of allergies.
Abbreviation key: HBV, hepatitis B virus; HCV, hepatitis C virus; MSM, men who have sex with men; PI, protease inhibitor; ZDV, zidovudine.
References:
  1. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005;40:1559-1585. [PubMed]
  2. D:A:D Study Group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: A multi-cohort collaboration. Lancet 2008;371:1417-1426. [PubMed]
  3. Strategies for Management of Anti-Retroviral Therapy/INSIGHT; DAD Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008;22:F17-24. [PubMed]
  4. Friis-Moller N, Reiss P, Sabin CA, et al. The DAD Study Group. Class of antiretroviral drugs and risk of myocardial infarction. N Engl J Med2007;356:1723-1735. [PubMed]
  5. Hirschtick RE, Glassroth J, Jordan MC, et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus. N Engl J Med1995;333:845-851. [PubMed]
  6. Horberg MA, Hurley LB, Klein DB, et al. Surgical outcomes in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. Arch Surg 2006;141:1238-1245. [PubMed]
  7. Tesoriero JM, Gieryic SM, Carrascal A, et al. Smoking among HIV positive New Yorkers: Prevalence frequency, and opportunities for cessation.AIDS Behav 2010;14:824-835. [PubMed]
  8. Niaura R, Shadel WG, Morrow K, et al. Human immunodeficiency virus infection, AIDS, and smoking cessation: The time is now. Clin Infect Dis2000;31:808-812. [PubMed]
  9. Guidelines for the Prevention of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from CDC, National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Morb Mortal Wkly Rep MMWR 2009;58(RR-4):1-207. Available at: http://aidsinfo.nih.gov/contentfiles/Adult_OI_041009.pdf
  10. Mohri N, Akamo Y, Mizokami M, et al. Perforated acute appendicitis in a patient with AIDS/HIV infection: Report of a case. Surg Today 1995;25:62-64. [PubMed]
  11. Kedzierska K, Rainbird MA, Lopez AF, et al. Effect of GM-CSF on HIV-1 replication in monocytes/macrophages in vivo and in vitro: A review. Vet Immunol Immunopathol 1998;63:111-121. [PubMed]
  12. Whetten K, Reif S, Napravnik S, et al. Substance abuse and symptoms of mental illness among HIV-positive persons in the Southeast. Southern Med J 2005;98:9-14. [PubMed]
  13. Substance Abuse and Mental Health Services Administration. Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings. Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4856Findings. Rockville, MD; 2010. Available at: http://www.gmhc.org/files/editor/file/a_pa_nat_drug_use_survey.pdf
  14. Diep BA, Chambers HF, Graber CJ, et al. Emergence of multi-drug resistant community associated methicillin resistant Staphylococcus aureus clone USA 300 in men who have sex with men. Ann Intern Med 2008;148:249-257. [PubMed]

Perioperative Medication Management

January 2012

RECOMMENDATIONS
  • Clinicians should continue ART in the perioperative period with as little interruption as possible, particularly for patients co-infected with hepatitis B virus (HBV) who are receiving an ART regimen that also has activity against HBV. When ART interruption is necessary, all components of the regimen should be stopped and clinicians should consult with a provider who has experience in management of ART. (AI)
  • For patients who require prophylaxis for Pneumocystis jirovecii (PCP) and are unable to receive oral medications for more than 1 week, TMP/SMX should be administered intravenously. If there is a contraindication to TMP/SMX, pentamidine should be administered intravenously or by inhalation. (AIII)
  • Patients with a history of MRSA colonization or infection should receive vancomycin instead of cefazolin for prophylaxis when indicated. (AIII)
  • Clinicians should assess for potential drug-drug interactions before new medications are introduced. (AIII)

Continuation of ART During the Perioperative Period

ART should be continued through the perioperative period with as little interruption as possible. This is particularly important for patients who are co-infected with HBV and receiving an ART regimen that also has activity against HBV; discontinuation of these medications may lead to a flare of the underlying hepatitis [1]. For patients who are unable to receive medications orally (NPO), a period of withholding ART will be necessary. When ART is withheld, all components of the regimen should be stopped.

TMP-SMX should be administered intravenously in individuals who require prophylaxis for Pneumocystis jirovecii pneumonia (PCP) but are NPO for more than 1 week. If TMP/SMX is contraindicated, pentamidine should be administered intravenously or by inhalation; however, aerosolized pentamidine may not be readily available and may be difficult to administer to patients who are intubated.

For patients who are able to receive liquids but not solids for more than 1 week, consideration should be given to converting the patient to an ART regimen that is available in liquid formulation. To ensure that the new regimen is fully suppressive, any changes to the ART regimen should only be done in consultation with a provider who has extensive experience in management of ART.

Potential Drug-Drug Interactions

RECOMMENDATION
  • Clinicians should consult a reliable drug interaction resource to identify potential interactions with antiretroviral medications, even for routine administration of commonly used medications in the perioperative period.

Potential for drug-drug interactions in patients receiving ART is increased due to the extensive cytochrome P450 interactions with both PIs and NNRTIs. Clinicians should assess for potential interactions before new medications are introduced.

In particular, caution should be used with anxiolytics and sedative/hypnotics, many of which have interactions with PIs that may be severe enough for their use to be contraindicated. For example, the common anesthesia medicine midazolam is contraindicated in combination with ritonavir. General anesthetics, such as halothane and enflurane, however, do not have significant interactions. Proton pump inhibitors, and to a lesser extent antacids and H2 blockers, may adversely affect the absorption of the PI atazanavir.

RESOURCES: DRUG-DRUG INTERACTIONS

The following websites provide information on antiretroviral drug interactions:

Wound Healing

Data are insufficient to determine whether wound healing is different in HIV-infected individuals receiving effective ART compared with non-HIV-infected individuals. At this time, standard recommendations should be followed for the use of perioperative antibiotics in the non-neutropenic HIV-infected patient.

References:
  1. Perillo RP. Acute flares in chronic hepatitis B: The natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001;120:1009-1022. [PubMed]

Postoperative Management

January 2012

RECOMMENDATIONS
  • HIV-infected patients should be mobilized postoperatively as soon as medically feasible because of increased risk of thromboembolic complications. (AII)
  • Clinicians should consider spontaneous pneumothorax in the differential diagnosis of acute onset dyspnea in patients with active PCP or a history of PCP. (AIII)
  • Clinicians should not withhold treatment for pain solely because a patient has a history of substance use. Rather, standard pain assessment and treatment protocols should be followed. (AII)

HIV-infected patients are at increased risk for hypercoagulability [1] and may be at increased risk for thromboembolic complications in the postoperative period. Appropriate implementation of prophylactic protocols and prompt mobilization as soon as medically feasible is particularly important in the HIV-infected population.

Spontaneous pneumothorax should be considered in the differential diagnosis of acute-onset dyspnea. HIV-infected patients with active PCP or a history of PCP are at increased risk for spontaneous pneumothorax; individuals at highest risk include those with obvious cystic lesions on chest x-ray and those undergoing mechanical ventilation [2]

Patients who are receiving methadone replacement therapy or who chronically use opiates may require increased doses of pain medication during the postoperative period. Management of pain in patients receiving buprenorphine/naloxone may be more challenging and should involve consultation with a pain management specialist. See Pain in the Substance User with HIV Infection.

References:
  1. Shen YM, Frenkel EP. Thrombosis and a hypercoagulable state in HIV-infected patients. Clin Appl Thromb Hemost 2004;10:277-280. [PubMed]
  2. Pastores SM, Garay SM, Naidich DP, et al. Review: Pneumothorax in patients with AIDS-related Pneumocystis carinii pneumonia. Am J Med Sci1996;312:229-234. [PubMed]

All Recommendations

Medical Care Criteria Committee, January 2012

ALL RECOMMENDATIONS: PERIOPERATIVE MANAGEMENT
Risk to the Surgical Team
  • Universal surgical precautions that apply to all patients should be followed. (AIII)
Preoperative Evaluation 
  • The preoperative evaluation of HIV-infected patients should be the same as that for non-HIV-infected patients; however, clinicians should carefully assess for the following conditions that are more prevalent in the HIV-infected population (AIII):
    • hepatic and renal dysfunction
    • coronary artery disease and cardiac risk
    • coagulopathy, thrombocytopenia, and neutropenia
    • active alcohol or substance use, including both prescription and non-prescription drug use
    • history of prior infection/colonization with methicillin-resistant Staphylococcus aureus (MRSA), particularly in men who have sex with men (MSM)
    • drug allergies
  • Clinicians should obtain urine toxicology, with patient consent, if the substance use history is unreliable and there are concerns about substance use. Elective surgery should be deferred until active substance use has been addressed. (AIII)
  • Individuals with a history of MRSA colonization or infection should receive vancomycin instead of cefazolin for prophylaxis when indicated. (AIII)
Perioperative Medication Management 
  • Clinicians should continue ART in the perioperative period with as little interruption as possible, particularly for patients co-infected with hepatitis B virus (HBV) who are receiving an ART regimen that also has activity against HBV. When ART interruption is necessary, all components of the regimen should be stopped and clinicians should consult with a provider who has experience in management of ART. (AI)
  • For patients who require prophylaxis for Pneumocystis jirovecii (PCP) and are unable to receive oral medications for more than 1 week, TMP/SMX should be administered intravenously. If there is a contraindication to TMP/SMX, pentamidine should be administered intravenously or by inhalation. (AIII)
  • Patients with a history of MRSA colonization or infection should receive vancomycin instead of cefazolin for prophylaxis when indicated. (AIII)
  • Clinicians should assess for potential drug-drug interactions before new medications are introduced. (AIII)
  • Clinicians should consult a reliable drug interaction resource to identify potential interactions with antiretroviral medications, even for routine administration of commonly used medications in the perioperative period.
Postoperative Management 
  • HIV-infected patients should be mobilized postoperatively as soon as medically feasible because of increased risk of thromboembolic complications. (AII)
  • Clinicians should consider spontaneous pneumothorax in the differential diagnosis of acute onset dyspnea in patients with active PCP or a history of PCP. (AIII)
  • Clinicians should not withhold treatment for pain solely because a patient has a history of substance use. Rather, standard pain assessment and treatment protocols should be followed. (AII)

Care of the Transgender Patient | with HIV Infection Guideline

Introduction

Medical Care Criteria Committee, April 2015

RECOMMENDATION
  • Clinicians providing services to HIV-infected transgender patients should integrate transgender treatment recommendations and standards of care into their practice. (AII)

Clinicians caring for HIV-infected patients may encounter individuals whose experienced gender does not conform to his/her natally assigned sex. These guidelines use the term transgender to refer to a broad range of nonconforming gender identities.

Some patients may be unsure of their gender identity and may not have had opportunities to discuss their concerns with a medical professional. Others may have a highly developed gender identity and may request hormone therapy or may already be receiving hormones that are obtained either by prescription or illicitly without a prescription.

Many HIV-infected transgender patients avoid healthcare providers because they fear insensitive treatment or have perceptions of being judged. Some of these patients also may have had poor interactions with previous providers. Providing a spectrum of care may help patients overcome resistance to treatment if these services are provided in a nonjudgmental manner. These services include:

  • HIV-related medical care that includes HIV prevention and harm reduction counseling
  • Mental health and substance use screening and services
  • Transgender-specific care, such as hormone therapy and case management services

As part of transgender-specific care, clinicians should integrate treatment recommendations and standards of care for transgender patients into their practice. For information regarding transgender standards of care, see Standards of Care and Referral Resources.

RESOURCES

Provision of transgender-related services in one setting is optimal. However, if such treatment integration is not possible, the clinician should make appropriate referrals for necessary specialized services, including transgender-related healthcare, community resources, and legal services (see Standards of Care and Referral Resources).

Epidemiology: Specific epidemiologic data for HIV-infected transgender individuals are lacking. However, a review of available data reported a mean HIV prevalence of 27.7% in male-to-females (MtFs) in four studies where HIV testing was performed in this population [1]. Seroprevalence was highest among black MtFs, with a mean estimate of 56.3% [1]. An HIV prevalence rate of 68% among MtF sex workers was also reported in a small sample population [1]. Limited data suggest that HIV prevalence rates among female-to-males (FtMs) is low, but their self-reported sexual risk behaviors suggest an increased risk for HIV infection compared with the general population [1].

Reference:
  1. Herbst JH, Jacobs ED, Finlayson TJ, et al. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: A systematic review. AIDS Behav 2008;12:1-17. [PubMed]

Terminology

April 2015

Knowledge of transgender-related terminology is important for awareness and effective communication with transgender patients. See below for an overview of commonly used transgender-related terms.

Transgender: An umbrella term for people whose gender identity extends beyond the conventional paradigms of birth-assigned sex, behavior, or appearance. The term may include, but is not limited to, people who identify as male-to-female (MtF) or female-to-male (FtM), cross-dressers, androgynous, and bi-gender individuals.

Male-to-Female (MtF) Transgender or Transfemale or Transwoman: An individual born with male anatomy whose gender identity is that of a woman. A MtF transgender person may or may not choose feminization enhancement treatments or may choose specific, instead of complete, enhancements. For example, the individual may choose to enlarge breasts but maintain male genitalia.

Female-to-Male (FtM) Transgender or Transmale or Transman: An individual born with female anatomy whose gender identity is that of a man. A FtM transgender person may or may not choose masculine enhancement treatments or may choose specific, instead of complete, enhancements.

Transsexual: An antiquated term that originated in the medical and psychological literature to describe someone who identifies as a member of the opposite anatomical sex. Many transgender people prefer the term transgender instead of transsexual, and, unlike transgender, transsexual is not an umbrella term to describe gender variation in an individual.

Intersex: A term applied to various conditions resulting from chromosomal anomalies and developmental disorders (e.g., androgen insensitivity syndrome and congenital adrenal hyperplasia) that result in impaired fertility, mixed sex characteristics, and, although rare, ambiguous genitalia. Intersex conditions are currently being redefined in the medical literature as disorders of sex development [1,2].

Cross-dresser: An individual who dresses as the opposite sex and may or may not seek physical changes. People may cross-dress for a variety of reasons, including for entertainment or theatrical purposes (e.g., drag queens and drag kings) or because dressing in clothes of the opposite sex provides self-gratification.

Androgynous: An individual who may appear to have few gender-defining characteristics or who may have characteristics of both sexes (e.g., bi-gender).

Bi-gender: An individual whose gender identity includes both sexes. Bi-gender individuals may switch between masculine and feminine gender roles.

Gender Identity Disorder: A Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM IV-TR) term that is used for the provision of transgender-related care and replaces the older term gender dysphoria. However, gender identity disorder is a controversial term within the transgender community, and clinicians should be sensitive to the negative effects that can result from classifying gender identity as a disorder.

Gender Transition: The process of bringing the body and mind into alignment. There are many aspects of transition that may occur simultaneously or sequentially. Transition includes physical (hormones, surgery), social, psychological, linguistic, intellectual, and spiritual aspects of self. The term transition should be used in place of sex change, pre-operative, or post-operative, because these latter terms inaccurately suggest that one must have surgery to truly change one’s sex [3].

Defamatory Terms: The terms transvestite, hermaphrodite, she-male, he-she, tranny, and gender-bender may be considered derogatory if used by someone who is not transgender [3]. (Note: although providers should not use these terms, transgender persons will sometimes use these terms as slang.)

KEY POINT
  • Gender identity is distinct from sexual orientation. Sexual orientation involves sexual attraction, whereas gender identity involves the individual’s natal sex in relation to the gender that he/she experiences.

Like all people, transgender individuals present with a variety of sexual orientations and behaviors. The terms gay, straight, lesbian, homosexual, andheterosexual may be defined differently by transgender individuals, depending on whether they are using their natal anatomy or their gender identity as a reference point. As with all people, these terms may be more about identity than behavior. Therefore, assessment of a patient’s gender identity is distinct from assessment of his/her sexual behavior (see Risk- and Harm-Reduction Approach).

References:
  1. Fenway Health. Glossary of Gender and Transgender Terms. Boston, MA; January 2010 Revision. Available at: www.fenwayhealth.org/site/DocServer/Handout_7-C_Glossary_of_Gender_and_Transgender_Terms__fi.pdf
  2. Feldman JL, Goldberg J. Transgender Primary Medical Care: Suggested Guidelines for Clinicians in British Columbia. Vancouver, British Columbia, Canada: Transcend Transgender Support & Education Society/Vancouver Coastal Health’s Transgender Health Program; 2006. Available at: http://transhealth.vch.ca/resources/library/tcpdocs/guidelines-primcare.pdf
  3. Gender Identity Project. Trans Basics: Glossary of Terms. New York, NY: The Lesbian, Gay, Bisexual & Transgender Community Center. Available at: http://www.gaycenter.org/gip/transbasics/glossary

Baseline History and Psychosocial Management

April 2015

RECOMMENDATION
  • As part of the routine management of HIV-infected patients, clinicians should perform a psychosocial assessment at baseline and at least annually in HIV-infected transgender patients. (AIII)

A psychosocial assessment is used to identify not only the transgender patient’s basic psychosocial information but also circumstances that may require transgender-related case management services (see below). Some patients may feel stigmatized or victimized by family members, coworkers, or employers. Such negative experiences often destabilize patients and can be barriers to HIV treatment.

A patient’s responses to a psychosocial assessment may also increase the clinician’s awareness of transgender-related culture, advocacy organizations, and social networks.

Transgender-Focused Psychosocial Assessment

Support network

  • Family and partner contacts, including level of knowledge and support of patient’s gender identity
  • Social connections and community networks (e.g., house ball community)
    • The house ball community is based primarily on communal support among gay and transgender individuals. The majority of members are black and Hispanic [1]. Approximately 40 houses, which often comprise a large extended family, exist in New York City.5 The houses organize events, or balls, that include a variety of performances and competitions between houses. For some individuals, membership to a house may provide support and encouragement and may be a source of relief from social isolation.
  • Stability in relationships

Transgender-related discrimination or violence

Housing status

Employment and insurance

  • If employed, are the patient’s employer and coworkers accepting of the patient’s gender identity? 
    • Employer support may lead to assistance in obtaining required documents to change gender identity on insurance and other legal documents.
  • If insured, can the patient be reimbursed for transgender-related care?

Educational level

Legal issues

  • Living will and healthcare proxy
  • Permanency planning for dependents
  • Potential obstacles to legal gender change and name change

For more information about psychosocial assessment, refer to the Quick Reference Guide to Mental Health Screening.

Reference:
  1. Murrill CS, Liu KL, Guilin V, et al. HIV prevalence and associated risk behaviors in New York City’s house ball community. Am J Public Health 2008;98:1074-1080. [PubMed]

Routine Screening and Lab Assessments

April 2015

RECOMMENDATION
  • Routine medical screening of HIV-infected transgender patients should be performed according to standards of care, as determined by clinical judgment and according to the patient’s level of comfort. (AIII)

For recommendations on cancer and cardiovascular screening for patients receiving hormone therapy, see Cross-Gender Therapy > Hormone Therapy.

Most aspects of routine medical screening in transgender patients are similar to those in the general population. However, transgender patients, regardless of their surgical status, may find aspects of a physical examination distressing or traumatic, particularly breast, genital, pelvic, and rectal examinations. When immediate examination is not clinically indicated, examination deferral can be offered until the patient expresses readiness. Deferral of examinations to increase patient comfort should be documented in the medical record. An ongoing dialogue about the patient’s concerns, as well as offering examination deferral when appropriate, may convey respect for the patient. Patients who perceive respect and encouragement from their care providers may be more proactive about their health and remain in care (see below) [1].

Strategies to help alleviate a patient’s concerns about physical examination:

  • Address the patient’s fears
  • Explain each step of the examination prior to performing it
  • Use the smallest, clinically indicated speculum for Pap tests and pelvic examinations
  • Use urine-based gonococcal/chlamydial testing for male-to-female patients
  • Offer self-collection of rectal and pharyngeal swabs for gonococcal/chlamydial testing
  • For extreme cases of anxiety (particularly in patients with a history of physical or sexual abuse):
    • Consider a referral for psychotherapy to decrease post-traumatic stress-type symptoms prior to physical examination
    • Consider administration of a low-dose anxiolytic prior to physical examination

Pelvic Examination

RECOMMENDATION
  • Clinicians should perform routine pelvic examinations in HIV-infected FtM patients and MtF patients who have undergone complete sex reassignment surgery according to HIV care guidelines for natal females. Before performing a pelvic examination in transgender patients, clinicians should explain the medical reasons for the examination. (AIII)

HIV-infected FtM patients remain at risk for gynecologic complications that can be detected by routine pelvic examinations (see Primary Care Approach to the HIV-Infected Patient).

Cytologic Screening

RECOMMENDATIONS
  • Clinicians should perform routine cervical Pap tests in any HIV-infected FtM patient with cervical tissue; patients who are uncomfortable receiving a Pap test should be educated about the importance of obtaining cervical cytology. (AIII)
  • Clinicians should notify the pathologist when submitting a Pap test sample from a FtM patient who is receiving testosterone therapy because testosterone-related atrophy of the cervix may mimic cervical dysplasia [2]. (AIII)
  • Anal Pap tests should be performed in HIV-infected transgender patients according to guidelines for natal males and natal females (see Anal Dysplasia and Cancer). (AIII)
  • Neovaginal Pap tests are not indicated for HIV-infected MtF patients. (AIII)

FtM patients should receive routine cervical Pap testing if cervical tissue is present, regardless of whether they have undergone a hysterectomy.

KEY POINT
FtM patients receiving testosterone therapy may experience atrophy of the cervix, which can mimic cervical dysplasia [2]. Notifying the pathologist of the patient’s testosterone treatment status can increase accuracy of Pap test results.

For transgender patients, the smallest, clinically indicated speculum may be necessary for a Pap test. For information regarding Pap screening, refer to Cervical Dysplasia and Cancer.

Screening for Gonococcal and Chlamydial Infections

RECOMMENDATIONS
  • Clinicians should screen HIV-infected transgender patients at baseline for gonorrhea and chlamydia; screening should also be performed at least annually thereafter for sexually active HIV-infected transgender patients. (AIII)
  • Clinicians should test all possible sites of exposure when screening for gonorrhea and chlamydia, including the urethra, rectum, and pharynx. (AIII)

For additional information regarding gonococcal and chlamydial infections in HIV-infected patients, refer to the CDC’s guidelines on gonococcal and chlamydial infections.

References:
  1. Aujoulat I, d’Hoore W, Deccache A. Patient empowerment in theory and practice: Polysemy or cacophony? Patient Educ Couns. 2007;66:13-20. [PubMed]
  2. Grynberg M, Fanchin R, Dubost G, et al. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod Biomed Online 2010;20:553-558. [PubMed]

Cross-Gender Therapy

April 2015

Cross-gender therapy is used to physically transition transgender patients and may include hormone therapy alone or hormone therapy and physical enhancements, such as breast enlargement or complete gender reassignment surgery. Cross-gender therapy provides the opportunity to greatly increase quality of life for transgender patients by physically affirming their gender identity. For clinicians caring for HIV-infected transgender patients, cross-gender therapy may also facilitate retention in HIV care. However, both hormone therapy and gender reassignment surgery require careful consideration, as well as patient education, to optimize safety and reduce health risks associated with these forms of treatment, including infertility.

Hormone Therapy

RECOMMENDATION
  • Clinicians should educate HIV-infected transgender patients about the possible health risks associated with hormone therapy. (AIII)

Although several small retrospective cohort studies suggest hormone therapy is generally safe, particularly over the short- and midterm [1], limited data exist on the long-term effects of cross-gender hormone therapy. Clinicians should inform patients that hormone therapy may increase the risk for:

  • Cardiovascular disease—particularly venous thromboembolism
  • Certain cancers—including breast, ovarian, and uterine cancers
  • Hepatic complications—due to disturbances in liver metabolism caused by elevated liver enzymes
  • Erectile dysfunction—due to increased circulating estrogen, which may also increase the risk for HIV transmission as a result of condom slippage or reduced condom use

Hormone treatment for transgender patients is most effective when clinicians provide therapy according to the fundamental principles listed below.

Feminizing Hormone Therapy

  • Basic goals: 
    • Provide estrogen as a feminizing agent
    • Provide androgen-blocking agents to decrease the effect of circulating testosterone
    • Maximize feminization
    • Minimize health risks
  • Basic effects: Over time and depending on hormone dose, some of these changes may be permanent; breast enlargement will not completely reverse after discontinuation of treatment
    • Integument:
      • Breast growth
      • Redistribution of body fat to a more gynecoid habitus (wider hips, narrowed waist)
      • Softening of skin
      • Decrease in body hair (facial hair generally diminishes to a lesser degree)
      • Slowing or stopping the androgenic hair loss
    • Genital:
      • Decreased sperm production and testicular size
      • Loss of fertility
      • Prostatic atrophy
      • Decreased libido
      • Less frequent, less firm erections (less firm erections can increase the risk for HIV and STI transmission due to condom slippage).
    • Other:
      • Decreased upper body strength
      • Feminizing hormones generally do not affect the size of the larynx or pitch of the voice

Masculinizing Hormone Therapy

  • Basic goals: 
    • Provide testosterone as a masculinizing agent
    • Maximize masculinization
    • Minimize health risks 
  • Basic effects: Many of these changes are reversible
    • Integument:
      • Redistribution of body fat to a more android habitus (loss of fat on hips, larger waist)
      • Growth of body and beard hair in accordance with the patient’s genetic predisposition
      • Male-pattern hair loss in accordance with the patient’s genetic predisposition
      • Minimal breast atrophy
    • Genital:
      • Clitoral hypertrophy
      • Irregular menses at first, then cessation of menses
      • Atrophic vaginitis
      • Increased libido
      • Loss of fertility
    • Other:
      • Deepened pitch of the voice
      • Increased upper body muscle size and strength, particularly with exercise

Concomitant Hormone Therapy and ART

RECOMMENDATIONS
  • Hormone therapy for HIV-infected transgender patients who are not initiating or receiving ART should be prescribed according to the same standards of care for all transgender patients. (AIII)
  • Before prescribing hormone therapy for HIV-infected transgender patients who are receiving
    ART, clinicians should (AIII):

    • Consult with, or refer patients, to a provider who has experience in prescribing both hormone therapy and ART to select appropriate hormone treatment
    • Educate patients about the prescribing considerations, including hormone selection and dose, for optimizing the effects of hormone therapy when prescribed in conjunction with an ART regimen
    • Discuss the importance of adherence to ART with patients, including the risks associated with dangerously high circulating hormone levels due to ART interruption
  • Clinicians should monitor hormone therapy in HIV-infected transgender patients according to established guidelines for all transgender patients. (AIII)

The clinician’s selection of hormone and dose depends on whether or not the patient is also receiving ART. For ART-naïve patients who are not initiating ART, hormone therapy can be provided in the primary care setting according to standard guidelines for all transgender patients, such as the guidelines published by the Endocrine Society [3]. Hormone therapy can also be provided through referral to another provider or an endocrinologist with expertise in transgender treatment. See Standards of Care and Referral Resources for medical referral resources for transgender patients.

Hormone therapy for patients initiating or already receiving ART requires a careful approach. Some transgender patients may decline ART because of concerns about reduced hormone levels when prescribed with HIV-related medications.

KEY POINT
  • Educating patients about how hormone selection and dose can reduce interactions between hormones and ART may encourage acceptance of ART from those who would otherwise decline it.

When hormone adjustments are made because of concomitant ART, concentrations of circulating hormone can become dangerously high if a patient does not adhere to ART. Severe cardiovascular complications, including stroke, deep vein thrombosis, and pulmonary embolism, may occur. Therefore, clinicians should consult with, or refer patients to, a provider who has experience in prescribing both hormone therapy and ART to select appropriate hormone treatment. Clinicians should also emphasize the risks associated with increased hormone levels when discussing the importance of adherence to ART.

KEY POINT
  • Cross-gender hormone monitoring for HIV-infected transgender patients is the same as for all transgender patients. Established monitoring guidelines, such as those by the Endocrine Society [3], should be used.

Cancer Screening and Hormone Therapy

Exogenous hormone therapy has been linked to breast, ovarian, and uterine cancers [4]. Estrogen therapy may reduce the risk for prostate cancer, although the extent of the reduction is unknown [4].

RECOMMENDATION
  • Clinicians should perform breast cancer screening in the following HIV-infected transgender patients according to clinical judgment and consideration of current guidelines established for natal females of the same age (see the appendix, Age Appropriate Diagnostic Screening):
    • FtM patients with remaining breast tissue (AIII)
    • MtF transgender patients with breast tissue who have received hormone therapy for at least 5 years (AIII)

Breast Cancer: MtF patients receiving feminizing hormones may be at increased risk for developing breast cancer in comparison with natal males. Although the risk is likely lower for MtF patients than it is for natal females [4], clinicians should educate MtF patients receiving feminizing hormones about the increased risk for breast cancer and about breast cancer screening. Screening should be performed for MtF patients who have received hormone therapy for at least 5 years and should be based on clinical judgment and consideration of current guidelines for natal females of the same age (see the appendix, Age Appropriate Diagnostic Screening).

The risk for breast cancer is reduced in FtM patients who have undergone chest reconstruction, including reduction or mastectomy. However, clinicians should inform patients that the risk is still present when breast tissue remains and should perform screening according to clinical judgment and consideration of current guidelines for natal females of the same age.

RECOMMENDATION

Prostate Cancer: Feminizing hormone therapy may reduce the risk for prostate cancer; however, the extent of the reduction is unknown [4]. Additional data are required before a transgender-specific recommendation can be established. 

Cardiovascular Disease and Hormone Therapy

RECOMMENDATION
  • When HIV-infected transgender patients choose to receive hormones, clinicians should educate them about the cardiovascular effects of hormone therapy and, when indicated, provide counseling to reduce the risk for cardiovascular disease; such discussions should take place at the time of initiation of hormone therapy and frequently thereafter. (AIII)

Both feminizing and masculinizing hormone therapies increase the risk for cardiovascular disease, including increased arterial stiffness with androgen therapy [5] and venous thromboembolism and stroke with estrogen therapy [1]. These effects should be discussed at the time of initiation of hormone therapy and frequently thereafter. Transgender patients receiving hormone therapy who have comorbid cardiovascular risk factors require more frequent counseling and education to reduce their risk for cardiovascular disease, including smoking (see the guideline, Smoking Cessation).

Gender-Confirming Surgery

RECOMMENDATIONS
  • The standards of care for gender reassignment surgery, as well as less complicated gender confirming procedures, are the same for HIV-infected transgender patients as for transgender patients who are not infected with HIV. (AIII)
  • Surgery, including breast implantation and gender-reassignment surgery, is not contraindicated in HIV-infected patients. (AIII)

Some HIV-infected transgender patients may elect to receive surgery as part of the transitional process. Gender-confirming surgery may involve complete gender reassignment surgery, also known as gender realignment surgery or sex reassignment surgery; or less complicated procedures, such as rhinoplasty or breast and gluteal implantation in combination with feminizing hormone therapy. In either case, the standards of care for these gender-confirming surgical procedures are the same for HIV-infected transgender patients as for transgender patients without HIV infection. Decisions regarding gender-confirming surgery should be made in consultation with a specialist in transgender surgery. See Standards of Care and Referral Resources for referral resources for individuals seeking gender-confirming surgery.

References:
  1. Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: Extensive personal experience. J Clin Endocrinol Metab 2008;93:19-25. [PubMed]
  2. National Network of Libraries of Medicine. Health Literacy. Bethesda, Md. Available at: http://nnlm.gov/outreach/consumer/hlthlit.html
  3. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009;94:3132-3154. [PubMed]
  4. Ettner, Eyler, Monstrey, eds. Principles of Transgender Medicine and Surgery. New York, NY: Haworth Press; 2007.
  5. Emi Y, Adachi M, Sasaki A, et al. Increased arterial stiffness in female-to-male transsexuals treated with androgen. J Obstet Gynaecol Res2008;34:890-897. [PubMed]

Mental Health and Substance Use Screening

April 2015

RECOMMENDATIONS
  • Clinicians should perform a mental health and substance use assessment in HIV-infected transgender patients at baseline and at least annually thereafter. (AIII)
  • Clinicians should refer HIV-infected transgender patients requiring mental health services to a psychiatrist or psychologist with knowledge and experience in transgender treatment. (AIII)
  • If the HIV-infected transgender patient’s substance use screening result is positive, or if the patient has a history of substance use, the clinician should re-evaluate the patient’s substance use at least quarterly. (AIII)
  • Clinicians should offer patients with active substance use/abuse problems referral to appropriate substance use treatment programs or other substance use services. (AIII)

Comorbid mental health and substance use disorders are more prevalent among HIV-infected patients [1] and sexual minorities [2,3] than the general population. In addition to the baseline history and psychosocial assessment, clinicians should perform mental health and substance use screening. Identification and stabilization of mental health and substance use disorders in transgender patients can help eliminate barriers to medical care, including HIV treatment, and enable patients to pursue gender transformation in a positive manner and under medical supervision.

When further assessment is warranted for transgender patients, clinicians should optimally be able to refer them to a mental health or substance use provider who is experienced with transgender care. If the clinician cannot make a direct referral, then he/she should be familiar with appropriate referral services (see Standards of Care and Referral Resources). For information about mental health and substance use screening, refer to Quick Reference Guide to Mental Health Screening and Screening and Ongoing Assessment for Substance Use.

References:
  1. Walkup J, Wei W, Sambamoorthi U, et al. Antidepressant treatment and adherence to combination antiretroviral therapy among patients with AIDS and diagnosed depression. Psychiatr Q 2008;79:43-53. [PubMed]
  2. Meyer IH. Prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: Conceptual issues and research evidence. Psychol Bull 2003;129:674-97. [PubMed]
  3. King M, Semlyen J, Tai SS, et al. A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people. BMC Psychiatry 2008;8:70. [PubMed]

Risk- and Harm-Reduction Approach

April 2015

RECOMMENDATIONS
  • Clinicians should assess for the following behaviors in HIV-infected transgender patients:
    • Silicone use
    • Hormones obtained without prescription, including specific hormones used
    • Needle-sharing among those who inject hormones, silicone, and/or drugs
    • Sexual risk behaviors
    • Genital taping
  • Clinicians should provide risk-reduction counseling and, when appropriate, harm-reduction counseling for HIV-infected transgender patients who report potentially harmful behaviors. Patients at risk for intentionally harming their genitalia require referral for psychiatric evaluation. (AIII)

Silicone Use

No recommendations exist for administering silicone injections as gender-confirming treatment. However, this dangerous method for altering one’s appearance is often available at silicone parties or pumping parties. Many transgender patients may have friends who have received injections without major complications, but serious complications usually arise later. Clinicians and patients should discuss the possible consequences of silicone use, which are often not immediate.

In addition to the risk for HIV and hepatitis transmission and bacteriological infections, clinicians should emphasize the long-term risks that are commonly associated with silicone injection:

  • Silicone can congeal over time, move to other parts of the body and cause subsequent disfigurement
  • Silicone injected into the breast can interfere with the interpretation of mammograms, and may increase a patient’s risk for undetected cancer in the future

Life-threatening injuries are less common but can occur. Migration of the substance outside of the injection site into the blood stream (i.e., silicone embolism syndrome) can cause respiratory failure [1]. Silicone used for illicit injections may be composed of materials other than medical-grade silicone.

Hormone Use

Some transgender patients obtain hormones without a prescription. To reduce possible interactions with HIV-related treatment, clinicians should inquire about patients’ use of nonprescribed hormones and should ask for specific information regarding the type of hormones patients are obtaining. Many clinicians will advise patients to avoid use of hormones that are obtained without a prescription and inform them of the risks associated with such behavior; however, such advice may not be acknowledged unless the provider is offering an alternative method for obtaining hormone therapy. An effective harm-reduction approach may be to encourage a reduction in the use of street hormones as the patient transitions to receiving only prescribed hormone therapy. The following are risks associated with receiving hormones that are not obtained under the care of a clinician:

  • Needle-sharing increases the risk for hepatitis B, hepatitis C, and HIV transmission
  • Bacterial infections can result from non-sterile technique/supplies
  • Liver damage, blood clotting problems, and deep vein thrombosis can result from inconsistent hormone dosing in illicit preparations
  • Some hormones that are obtained without a prescription could be harmful in themselves (e.g., risk for disfigurement from cooking oil added to the illicit preparation)

Some providers periodically assess testosterone and estradiol levels to determine whether excess concentrations of the hormones are present (CIII). However, hormone levels may not provide a clear indication of the patient’s hormone use, particularly if procurement of hormones without a prescription is inconsistent. Other laboratory markers, such as prolactin for patients receiving estrogen or hematocrit for patients receiving testosterone, may be useful for monitoring hormone effects (CIII).

Injection Practices

For patients who engage in high-risk injection behaviors, harm-reduction techniques can offer an effective means for modifying behaviors that place patients at risk for transmission of HIV and other diseases. For example, transgender patients who choose to continue to inject illicit hormones or silicone should be referred to New York State’s Syringe Access Resources. Individuals seeking syringes for hormone injections should receive prescriptions for clean syringes and needles or referral to services that provide syringes appropriate for hormone injections and education about how to safely perform these injections. For additional information, see NYSDOH Syringe Access and Disposal; see Working with the Active User for information on safer injection techniques.

Sexual Risk

For all patients, a sexual risk assessment should focus on behaviors rather than the sexual orientation of the patient. In particular, the patient may not identify with the words homosexual or gay, and questions such as Are you a homosexual? or Are you gay? may not provide useful information. Clinicians should also strive to help the patient feel comfortable with providing information about his/her sexual behavior. The following could be used as part of a dialogue about sexual health:

  • I want to offer you the highest quality of care possible. Understanding your sexual practices will help me provide you with better care.
  • Do you have anal, oral, or vaginal sex?
  • Is this sex receptive, insertive, or both?
  • Do you use safer sex practices, such as wearing condoms and using dental dams?

Providers should use language that the individual patient understands. 

Genital Taping or Tucking

Some patients may attempt to hide their genitalia by taping or tucking. Taping increases the risk for urinary tract infections, as well as sores and damaged tissue, particularly when materials that can tear skin easily are used, such as duct tape. Patients whose long-term goals include sex reassignment surgery may reduce such behavior if they are educated about the reconstruction of natal genitalia to create new genitalia during sex reassignment surgery. If the clinician suspects that a patient may be at risk for intentionally harming his/her genitalia, then referral for a psychiatric evaluation is necessary.

Reference:
  1. Schmid A, Tzur A, Leshko L, et al. Silicone embolism syndrome: A case report, review of the literature, and comparison with fat embolism syndrome. Chest. 2005;127:2276-2281. [PubMed]

Case Management

April 2015

RECOMMENDATION
  • Case managers who provide services to HIV-infected transgender patients should:
    • Develop expertise in transgender-related services, such as assisting patients with access to healthcare, assisting with adherence to medical treatment and medical appointments, and making appropriate referrals
    • Closely monitor changes in contact information, housing, and psychosocial support for patients with unstable living situations
    • Develop awareness of “trans-friendly” resources, including education, employment, legal aid resources, and harm-reduction programs
    • Be familiar with the resources available to assist patients with obtaining a change of name and gender status on their identification and health insurance cards (AIII)

Unstable living situations or difficulties with insurance reimbursement may complicate regular access to healthcare for HIV-infected transgender patients. Such challenges require proactive case management involving familiarity with transgender-related services. Case managers with such expertise can facilitate care for transgender patients by performing the following functions:

  • Closely monitor changes in contact information, housing, and psychosocial support for patients with unstable living situations
  • Assist with adherence to medical treatment and appointments
  • Refer patients to appropriate transgender-related resources

Access to trans-friendly programs may facilitate referrals for housing, employment, harm-reduction programs, and legal aid resources when needed (see Standards of Care and Referral Resources). Case managers should be able to assist with name and gender status change for transgender patients’ identification cards and health insurance.

Members of the care team may find it beneficial to guide patients through the process of gender change before name change because changing the patient’s gender on his/her health insurance ID card may enable reimbursement for hormone treatment. This step may help prevent patients from obtaining illicit hormones. Advocacy for coordination of transgender-related health benefits may be necessary. (Third-party reimbursement programs, including Medicaid, the New York State AIDS Drug Assistance Program (ADAP), and private insurers, may require female and male gender designations on insurance identification before payment can be issued for feminizing and masculinizing hormone therapy, respectively.)

Case managers can develop expertise in managing the processes described above through participation in training programs and related professional development. For organizations that can assist in transgender legal issues, see Standards of Care and Referral Resources.

 

Standards of Care and Referral Sources

April 2015

Standards of Care

The most recognized transgender-related standards of care are the World Professional Association for Transgender Health (WPATH) Standards of Care, formerly known as the Harry Benjamin International Gender Dysphoria Association Standards of Care (www.wpath.org) [1]. This publication provides clinicians who may not be familiar with transgender treatment with a framework for many clinical decisions. 

The WPATH Standards of Care Provides a comprehensive description of the “Five Elements of Treatment”: 1) diagnostic assessment, 2) psychotherapy, 3) real-life experience, 4) hormone therapy, and 5) surgical therapy. The Standards of Care also serve as a resource for related treatment information, including hormonal treatment and surgical options.

Other organizations have developed guidelines that expand on the WPATH Standards of Care; these include collaborative projects involving experts in the medical care of transgender patients and those with knowledge of the psychosocial aspects of transgender care, such as the following:

  • Principles of Transgender Medicine and Surgery [2]
  • Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice [3]
  • Transgender Primary Medical Care: Suggested Guidelines for Clinicians in British Columbia [4]

Informational Resources

Clinicians can refer to a number of organizations for comprehensive transgender-related medical information. These organizations also provide additional transgender-related resources.

Referral Resources for Transgender Care and Services

Resources are available for clinicians to connect patients with a variety of transgender-related services.

Transgender-Related Conferences

A number of transgender-related conferences take place annually. Some of these conferences include:

References:
  1. World Professional Association for Transgender Health (formerly the Harry Benjamin International Gender Dysphoria Association). WPATH Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. Minneapolis, MN: World Professional Association for Transgender Health. Available at: www.wpath.org
  2. Ettner, Eyler, Monstrey, eds. Principles of Transgender Medicine and Surgery. New York, NY: Haworth Press; 2007.
  3. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009;94:3132-3154. [PubMed]
  4. Feldman JL, Goldberg J. Transgender Primary Medical Care: Suggested Guidelines for Clinicians in British Columbia. Vancouver, British Columbia, Canada: Transcend Transgender Support & Education Society/Vancouver Coastal Health’s Transgender Health Program; 2006.

All Recommendations

Medical Care Criteria Committee, April 2015

ALL RECOMMENDATIONS: CARE OF THE HIV-INFECTED TRANSGENDER PATIENT
Introduction 
  • Clinicians providing services to HIV-infected transgender patients should integrate transgender treatment recommendations and standards of care into their practice. (AII)
Baseline History and Psychosocial Management 
  • As part of the routine management of HIV-infected patients, clinicians should perform a psychosocial assessment at baseline and at least annually in HIV-infected transgender patients. (AIII)
Routine Screening and Lab Assessments 
  • Routine medical screening of HIV-infected transgender patients should be performed according to standards of care, as determined by clinical judgment and according to the patient’s level of comfort. (AIII)
  • Clinicians should perform routine pelvic examinations in HIV-infected FtM patients and MtF patients who have undergone complete sex reassignment surgery according to HIV care guidelines for natal females. Before performing a pelvic examination in transgender patients, clinicians should explain the medical reasons for the examination. (AIII)
  • Clinicians should perform routine cervical Pap tests in any HIV-infected FtM patient with cervical tissue; patients who are uncomfortable receiving a Pap test should be educated about the importance of obtaining cervical cytology. (AIII)
  • Clinicians should notify the pathologist when submitting a Pap test sample from a FtM patient who is receiving testosterone therapy because testosterone-related atrophy of the cervix may mimic cervical dysplasia. (AIII)
  • Anal Pap tests should be performed in HIV-infected transgender patients according to guidelines for natal males and natal females (see Anal Dysplasia and Cancer). (AIII)
  • Neovaginal Pap tests are not indicated for HIV-infected MtF patients. (AIII)
  • Clinicians should screen HIV-infected transgender patients at baseline for gonorrhea and chlamydia; screening should also be performed at least annually thereafter for sexually active HIV-infected transgender patients. (AIII)
  • Clinicians should test all possible sites of exposure when screening for gonorrhea and chlamydia, including the urethra, rectum, and pharynx. (AIII)
Cross-Gender Therapy
  • Clinicians should educate HIV-infected transgender patients about the possible health risks associated with hormone therapy. (AIII)
  • Hormone therapy for HIV-infected transgender patients who are not initiating or receiving ART should be prescribed according to the same standards of care for all transgender patients. (AIII)
  • Before prescribing hormone therapy for HIV-infected transgender patients who are receiving
    ART, clinicians should (AIII):

    • Consult with, or refer patients, to a provider who has experience in prescribing both hormone therapy and ART to select appropriate hormone treatment
    • Educate patients about the prescribing considerations, including hormone selection and dose, for optimizing the effects of hormone therapy when prescribed in conjunction with an ART regimen
    • Discuss the importance of adherence to ART with patients, including the risks associated with dangerously high circulating hormone levels due to ART interruption
  • Clinicians should monitor hormone therapy in HIV-infected transgender patients according to established guidelines for all transgender patients. (AIII)
  • Clinicians should perform breast cancer screening in the following HIV-infected transgender patients according to clinical judgment and consideration of current guidelines established for natal females of the same age (see the appendix, Age Appropriate Diagnostic Screening):
    • FtM patients with remaining breast tissue (AIII)
    • MtF transgender patients with breast tissue who have received hormone therapy for at least 5 years (AIII)
  • Clinicians should perform digital rectal examinations as part of routine HIV care for HIV-MtF transgender patients (see Primary Care Approach to the HIV-Infected Patient); clinical judgment and current guidelines for natal HIV-infected males should be used when considering prostate examinations in MtF transgender patients. (AIII)
  • When HIV-infected transgender patients choose to receive hormones, clinicians should educate them about the cardiovascular effects of hormone therapy and, when indicated, provide counseling to reduce the risk for cardiovascular disease; such discussions should take place at the time of initiation of hormone therapy and frequently thereafter. (AIII)
  • The standards of care for gender reassignment surgery, as well as less complicated gender confirming procedures, are the same for HIV-infected transgender patients as for transgender patients who are not infected with HIV. (AIII)
  • Surgery, including breast implantation and gender-reassignment surgery, is not contraindicated in HIV-infected patients. (AIII)
Mental Health and Substance Use Screening 
  • Clinicians should perform a mental health and substance use assessment in HIV-infected transgender patients at baseline and at least annually thereafter. (AIII)
  • Clinicians should refer HIV-infected transgender patients requiring mental health services to a psychiatrist or psychologist with knowledge and experience in transgender treatment. (AIII)
  • If the HIV-infected transgender patient’s substance use screening result is positive, or if the patient has a history of substance use, the clinician should re-evaluate the patient’s substance use at least quarterly. (AIII)
  • Clinicians should offer patients with active substance use/abuse problems referral to appropriate substance use treatment programs or other substance use services. (AIII)
Risk- and Harm-Reduction Approach
  • Clinicians should assess for the following behaviors in HIV-infected transgender patients:
    • Silicone use
    • Hormones obtained without prescription, including specific hormones used
    • Needle-sharing among those who inject hormones, silicone, and/or drugs
    • Sexual risk behaviors
    • Genital taping
  • Clinicians should provide risk-reduction counseling and, when appropriate, harm-reduction counseling for HIV-infected transgender patients who report potentially harmful behaviors. Patients at risk for intentionally harming their genitalia require referral for psychiatric evaluation. (AIII)
  • Case managers who provide services to HIV-infected transgender patients should:
    • Develop expertise in transgender-related services, such as assisting patients with access to healthcare, assisting with adherence to medical treatment and medical appointments, and making appropriate referrals
    • Closely monitor changes in contact information, housing, and psychosocial support for patients with unstable living situations
    • Develop awareness of “trans-friendly” resources, including education, employment, legal aid resources, and harm-reduction programs
    • Be familiar with the resources available to assist patients with obtaining a change of name and gender status on their identification and health insurance cards (AIII)

 

HIV Infection in Older Adults | (Quick Reference Guide)

Introduction

HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians 

Medical Care Criteria Committee, April 2015

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Effective antiretroviral therapy (ART) has prolonged the lifespan of people living with HIV. Non-HIV/AIDS-related conditions now account for most morbidity and mortality among older people with HIV infection. Although ART reduces the effects of HIV disease and chronic inflammation, it does not restore normal immunologic function. The literature describes an aging HIV-infected population (between 50-65 years of age) with high rates of comorbid conditions compared with their non-HIV-infected counterparts. Medical care may be further complicated by neurocognitive decline and high rates of depression, alcohol and substance use, and social isolation. The goals of caring for older people with HIV infection are to minimize illness and frailty, optimize health and well-being, and prolong life.

This reference guide for care of older adults with HIV supplements, but does not replace, standard guidelines for all adults with HIV found on this website.

KEY POINTS
  • People with HIV may develop chronic diseases associated with aging earlier in life, resulting in the development of multiple comorbid conditions.
  • Aging can compound the immunological impact of HIV and accelerate HIV disease progression.
  • Older people with HIV are at particular risk for polypharmacy, which increases the risk of drug-drug interactions and adverse events; it also can negatively affect cognitive function and quality of life.

To prevent or delay disability, the following assessments are particularly important for older adults with HIV/AIDS:

  • Total HIV and non-HIV disease burden and functional status
  • Medication adherence, side effects, drug-drug interactions, need for dose adjustments
  • Alcohol and substance use, including prescription drugs
  • Mental and cognitive status
  • Social support
RESOURCES

Total Disease Burden and Functional Status

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

April 2015

Assess:

  • Disease progression since last visit
  • Consultations, specialty care visits, oral health care, ancillary tests, changes in medications
  • New symptoms and diagnoses
  • Changes in hearing and sight
  • Basic and instrumental activities of daily living (ADLs)
  • Pain, range of motion, gait
  • Frailty
  • Need for home care, assisted or congregate living, skilled nursing, or hospice services
  • Hygiene: hair, nails, feet
Screening Tools
  • Osteoporosis: Bone density, vitamin D
  • Cardiovascular disease risk: Framingham risk score assessment, lipid profile including total cholesterol, HDL, LDL, and triglycerides (at least annually, repeat before initiating ART, and within 4 to 8 months after initiating)
  • Activities of daily living [a]: Ask patient and/or caregivers whether patient can perform the following activities with or without assistance from others or from assistive devices:
    • Basic ADLs: Feeding, toileting, continence, bathing, grooming, dressing, ambulation, transfers (to or from bed or chair)
    • Instrumental ADLs: Telephone, shopping, food preparation, housekeeping, laundry, transportation, medication management, financial management
  • Pain, range of motion, gait: Note whether patient is impaired by pain, joint stiffness, or abnormal or unsteady gait and is at risk for falls
  • Frailty [b]:Using a phenotype assessment, frailty is indicated by the presence of three or more of the following five factors. 
    • Shrinking: unintentional weight loss (>10 lbs in prior year)
    • Weakness: as determined by grip strength
    • Poor endurance and energy: self-report of exhaustion
    • Slowness: more than 6-7 seconds (depending on height) to walk 15 ft
    • Decreasing physical activity
  • HIV disease progression [c]: The VACS Index, a prognostic tool based on a calculation of age and eight routine laboratory tests, helps monitor HIV disease progression and response to therapy. An online calculator can be accessed at: http//vacs.med.yale.edu

Notes:

  1. Based on 1) Katz S. Assessing self-maintenance: Activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc 1983;31:721-727. 2) Lawton MP, et al. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179-186.
  2. For the full validated assessment, refer to Fried LP, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-M156.
  3. Justice AC, et al. Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: A North American cross cohort analysis. J Acquir Immune Defic Syndr 2013;62:149-163.

Initiation of ART in Patients Over 50

Medical Care Criteria Committee April 2015

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

RECOMMENDATION
  • All patients, regardless of CD4 count, should be evaluated for ART. Patients >50 years of age are a high-risk group for whom initiation of ART is particularly urgent.
  • Older untreated HIV-infected persons have more rapid disease progression than younger persons [1].
  • Immunologic response is less robust in older patients [2-3]; however, patients >50 years of age who initiate therapy with higher CD4 counts are more likely to achieve better immunologic responses [4].
  • Patients who have longstanding HIV infection have increased susceptibility to inflammation-induced diseases and have diminished capacity to fight certain diseases [5].
References:
  1. Phillips A, et al. Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naïve individuals and those treated in the monotherapy era. AIDS 2004;18:51-58.
  2. Gras L, et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. J Acquir Immune Defic Syndr 2007;45:183-192.
  3. COHERE Study Group. Response to combination antiretroviral therapy: Variation by age. AIDS 2008;22:1463-1473.
  4. Li X, et al. CD4+T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy. J Acquir Immune Defic Syndr2011;57:421-428.
  5. Fauci A. NIH statement on National HIV/AIDS, www.nih.gov/news/health/sep2010/niaid-09.htm

Polypharmacy

April 2015

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

Polypharmacy significantly increases the chances of serious drug-drug interactions, toxicity, and poor adherence.

RECOMMENDATIONS
  • Perform medication review at every visit
  • Discontinue medications that are no longer needed
  • Encourage patients to use one pharmacy
  • Consider obtaining a dispensing history from the pharmacy

Assess:

  • Current medications and adherence
  • Potential drug interactions, adverse drug effects, allergies
  • Dosing considerations: renal and hepatic function, pharmacokinetic changes with aging

Note: When patients report use of erectile dysfunction medications or products to relieve vaginal dryness, clinicians should use the opportunity to discuss safer-sex practices.

Screening tools: Urine screen; blood panel

Medication list and adherence verification:

  • Create/update medication list, including over-the-counter drugs, supplements, and complementary and alternative medications.
  • Verify current pharmacy and check prescription pattern and fill dates.
  • Ask patients to bring pill bottles to visits, compare with medication list, and perform pill counts.
  • Cross-reference information with home health agency or other caregivers.
  • Consider use of customized pill cards, pill boxes (for those who can fill them on their own), home delivery, prepackaging of medication, “easy-open” containers.
  • Ensure that instructions on medication dosing are appropriately conveyed.

Conditions of aging that may affect adherence:

  • Impaired hearing: Perform screening test to determine need for formal testing
  • Impaired vision: Perform vision screening every 1-2 years in pts >65; every 1-3 years in pts 55-64; annually for pts with CD4
  • Cognitive impairment: Assess cognitive function at baseline and at least annually*
  • Polypharmacy (higher pill burden, greater cumulative side effects, medication fatigue): Perform medication review at every visit; discontinue medications that are no longer needed
  • Social isolation and lack of support: Assess social support at least annually*
  • Depression: Screen for depression at every visit*
  • Substance use, including misuse of prescriptions: Screen for substance use at baseline and at least annually

*See next sections for sample screening tools and questions.

Alcohol and Substance Use

April 2015

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

Patients >50 years of age are at risk for misuse of prescription drugs. As with all HIV-infected patients, clinicians should screen for alcohol and substance use at baseline and at least annually.

Signs of possible abuse of prescription medications (adapted from the Mayo Clinic):

  • Frequent reports of “losing” prescriptions and requests for more to be written
  • Seeking prescriptions from more than one doctor
  • Taking higher doses than prescribed
  • Mood swings
  • Change in sleep patterns
  • Poor decision-making

See Substance Use Screening: A Quick Reference Guide for HIV Primary Care Clinicians.

Mental Health and Cognitive Status

April 2015

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

As with all HIV-infected patients, clinicians should perform a comprehensive mental health screening at baseline and at least annually.

Assess:

  • Depression, anxiety, PTSD
  • Psychiatric history
  • Cognitive function
  • Suicidal/violent ideation
  • Sleep habits and appetite
  • Psychosocial status

Screening tools for cognitive function and depression are provided.

See Quick Reference Guide to Mental Health Screening for sample screening tools for all components of the comprehensive mental health screening.

Cognitive Function Screening Tool: International HIV Dementia Scale (IHDS)

Memory-Registration: Give 4 words to recall (dog, hat, bean, red)-1 second to say each. Then ask the patient all 4 words after you have said them. Repeat the words if the patient does not recall them all immediately. Tell the patient you will ask for recall of the words again a bit later.

1. Motor Speed: Have the patient tap the first two fingers of the non-dominant hand as widely and as quickly as possible.

Score:

  • 4 = 15 in 5 seconds
  • 3 = 11-14 in 5 seconds
  • 2 = 7-10 in 5 seconds
  • 1 = 3-6 in 5 seconds
  • 0 = 0-2 in 5 seconds

2. Psychomotor Speed: Have the patient perform the following movements with the non-dominant hand as quickly as possible:

  • Clench hand in fist on flat surface.
  • Put hand flat on surface with palm down.
  • Put perpendicular to flat surface on the side of the 5th digit.
  • Demonstrate and have the patient perform twice for practice.

3. Memory Recall: Ask the patient to recall the 4 words. For words not recalled, prompt with a semantic clue as follows: animal (dog); piece of clothing (hat); vegetable (bean); color (red).

Score: Give 1 point for each word spontaneously recalled. Give 0.5 point for each correct answer after prompting. (Maximum: 4 points)

Total Score: This is the sum of the scores on items 1–3. The maximum possible score is 12. Patients with a score of ≤10 should be evaluated further for possible dementia.

Note: Reprinted by permission of Wolters Kluwer Health. Sacktor NC, Wong M, Nakasujja N, et al. The International HIV Dementia Scale: A new rapid screening test for HIV dementia. AIDS 2005;19:1367-1374.

Questions to Identify Depression (PHQ-2)

Over the past 2 weeks, how often have you been bothered by any of the following problems?

  1. Little interest or pleasure in doing things:
    0 = Not at all
    1 = Several days
    2 = More than half the days
    3 = Nearly every day
  2. Feeling down, depressed, or hopeless:
    0 = Not at all
    1 = Several days
    2 = More than half the days
    3 = Nearly every day

Score: A score of 3 or more indicates the need for further evaluation

Note: Reprinted from Kroenke K, et al. The Patient Health Questionnaire-2: Validity of a two-item depression screener. Med Care 2003;41:1284-1292.

Social Support and Daily Care

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

Updated April 2015

Update:

  • Emergency contact information
  • Name of case manager, care coordinator, agencies providing services
  • Need for interpreter, family conference, advance directives, long-term care, or hospice discussion
  • HIPAA consents for communicating with support network

Sample Screening Questions

Social/household support:

  • Do you do things socially with friends? What do you like to do?
  • Is there anyone who could come with you to medical appointments?
  • Is there anyone who you would call if you felt really sick?
  • Does anyone help you shop, cook, do the laundry, or take care of the house?

Nutrition: How often do you eat? What do you eat for breakfast? Lunch? Dinner?

Mobility:

  • What do you do for exercise? How often to do you leave the house?
  • Do you ever use a cane, walker, or wheelchair?
  • Do you drive? Do you use the subway, buses, or taxis? Can you manage stairs?
  • Do you have friends or family members who could help with transportation?

Safety:

  • Have you ever fallen in your home or outside? Do you ever feel that you might?
  • Is your telephone always working? Do you have a phone in your bedroom?
  • Currently, does anyone hit you, bully you, or yell at you? Do you feel safe in your home and neighborhood?
  • Do you manage your own money? Do you think that anyone is stealing from you or taking advantage of you financially?

Communicating with Older Patients

Note: This material is from HIV in Older Adults: A Quick Reference Guide for HIV Primary Care Clinicians [Download PDF]

Updated April 2015

Establish rapport:

  • Use respectful, preferred forms of address
  • Engage the patient: maintain eye contact; use frequent, brief, affirmative responses; avoid rushing and interrupting; demonstrate empathy

Compensate for vision and hearing deficits:

  • Ensure patients are wearing eyeglasses and/or working hearing aids, if needed
  • Speak slowly and clearly; keep hands away from face
  • Use large type, visual aids

Create opportunity for discussion of sex:

  • Ask whether the patient is sexually active and has any problems to address
  • Assess and enhance patient’s knowledge of safer-sex practices

Ensure understanding:

  • Write down important information
  • Avoid jargon, ask if clarification is needed
  • Summarize plan and next steps

Derived from The National Institute on Aging. Talking with your older patient: A Clinician’s Handbook. NIH Pub No. 08-7105. September 2011. Accessed 2016 Aug 16. www.nia.nih.gov/sites/default/files/talking_with_your_older_patient.pdf

Discussing long-term care and hospice:

  • Establish a supportive relationship, acknowledge patient feelings and concerns, and offer reassurance
  • Identify and include other decision makers
  • Help define expectations based on disease status and prognosis
  • Discuss service needs, recommend level of care (home care, assisted living, skilled nursing, hospice), and establish consensus for treatment plan

Derived from 1) Balaban RB. A physician’s guide to talking about end-of-life care. J Gen Intern Med 2000;15:195-200. 2) Casarett DJ, et al. “I’m not ready for hospice”: Strategies for timely and effective hospice discussions. Ann Intern Med 2007;146:443-449.

Care of Older Women | with HIV Infection Guideline

HIV-Infection in Women Over 50

Women With HIV Infection Guidelines Committee, May 2009

Information about HIV-infected women over the age of 50 and their treatment is limited because few studies have targeted this gender and age group. However, some generalizations have been observed in clinical studies, including the following:

  • Before the use of HAART, older age was a predictor for an increased rate of disease progression to AIDS and death [1,2]. The age factor can be mitigated by appropriate treatment with HAART [3,4].
  • HIV-related symptoms and side effects of HIV-related medications may be difficult to distinguish from common age-related comorbidities, such as anemia, wasting, dyspnea on exertion, rheumatologic disorders [5], dementia, osteoporosis, lipid abnormalities, and insulin resistance.
  • Because of the increased incidence of malignancy in HIV-infected adults [6] and the increased incidence and association of some malignancies with aging, clinicians need to be vigilant for vulvar and cervical neoplasia (see Anogenital Neoplasia) and ovarian, breast, and uterine cancer in older women.

This chapter discusses prevalence and identification of HIV in women over the age of 50, primary health care for HIV-infected older women, the implications of initiating HAART and/or hormone replacement therapy (HRT), and the psychosocial issues that may affect older women living with HIV infection. The medical care for HIV-infected menopausal women and women over the age of 50 also includes the same elements of routine medical care that are appropriate for HIV-infected persons in general.

References:
  1. Phillips AN, Lee CA, Elford J, et al. More rapid progression to AIDS in older HIV-infected people: The role of CD4+ T-cell counts. J Acquir Immune Defic Syndr 1991;4:970-975.
  2. Adler WH, Baskar PV, Chrest FJ, et al. HIV infection and aging: Mechanisms to explain the accelerated rate of progression in the older patient. Mech Ageing Dev 1997;96:137-155.
  3. Cuzin L, Delpierre C, Gerard S, et al. Immunological and clinical responses to highly active antiretroviral therapy in patients with HIV infection aged > 50 years. Clin Infect Dis 2007;45:654-657. 
  4. Casau NC. Perspective on HIV infection and aging: emerging research on the horizon. Clin Infect Dis 2005;41:855-863. 
  5. Casado E, Olive A, Holgado S, et al. Musculoskeletal manifestations in patients positive for human immunodeficiency virus: Correlation with CD4 count. J Rheumatol 2001;28:802-804. 
  6. Gallagher B, Wang Z, Schymura M, et al. Cancer incidence in New York State Acquired Immunodeficiency Syndrome Patients. Amer J Epi 2001;154:544-556. 

Identification and Prevention of HIV Infection

May 2009

The number of older women with HIV infection is expected to increase for two reasons: 1) the rate and incidence of new infections in this age group are increasing [1], and 2) women already in care for HIV infection are expected to live longer due to improved ARV therapy and other treatment advances.

Risk Assessment and Risk-Reduction Counseling

RECOMMENDATION
  • Clinicians should discuss sexual and other risk behaviors and HIV prevention education at routine clinical visits for all HIV-infected women, regardless of age.

Women of all ages who are sexually active should receive risk-reduction counseling and education to prevent HIV transmission [2]. The need to discuss sexual risk behaviors with older women is supported by the following data. In New York State during 2005, women over the age of 50 comprised: 

  • 267 of 1,289 women with new HIV diagnoses (21%)
  • 356 of 1,564 women with new AIDS diagnoses (23%)
  • 2,296 of 13,712 women living with HIV (22%)
  • 6,057 of 20,600 women living with AIDS (29%)

Healthcare providers may be reluctant to discuss HIV risk behaviors with older women because it is assumed that these women are not sexually active or have conservative behaviors. Many older women do not perceive themselves as being at risk and may be uncomfortable inquiring about HIV infection. Women of all ages should receive risk assessments and risk-reduction counseling to prevent HIV transmission [2].

Risk-reduction counseling for the prevention of STI and HIV transmission should include use of condoms. Some older women may not want to use condoms because they experience vaginal irritation from dryness due to atrophic vaginitis, which can occur with decreasing hormone levels during menopause. However, condom use may be particularly important for these patients because atrophic vaginitis may increase mucosal viral transmission of HIV [3].

KEY POINT
  • Use of water-based lubricants and treatment with vaginal estrogen preparations, which are considered safe and effective, can decrease the discomfort that some older women may experience with condom use [4].

Identification of Acute Retroviral Syndrome and New Diagnoses in Older Women

RECOMMENDATION
  • Clinicians should consider acute retroviral syndrome in the differential diagnosis for older women who present with flu-like illnesses.

Older women may present with symptoms of acute retroviral syndrome, which may be dismissed as being associated with other age-related conditions, such as menopause or diabetes. Because the risk for new HIV infection in women over the age of 50 is often underestimated, clinicians need to be vigilant for older women who present in primary care with the acute retroviral syndrome. HIV should be part of the differential diagnosis for flu-like illnesses, and HIV testing should be performed. For recommendations on testing for acute HIV infection and management of patients with acute HIV infection, see Diagnosis and Management of Acute HIV Infection.

References:
  1. Centers for Disease Control and Prevention. Division of HIV/AIDS Prevention. United States HIV&AIDS Statistics by Age. HIV/AIDS Surveillance Report 2001;13(1). Available at: https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2001-vol-13-1.pdf
  2. Lieberman R. HIV in older Americans: An epidemiologic perspective. J Midwifery Womens Health 2000;45:176-182. Review.
  3. Dwyer JM, Penny R, Gatenby PA, et al. Susceptibility of postmenopausal women to infection with HIV during vaginal intercourse. Med J Aust 1990;153:299.
  4. The North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause 2007;14:355-356.

Routine Primary Healthcare

May 2009

Although many clinicians focus primarily on the complexities of managing HIV disease, general primary care guidelines for older women should also be implemented, including age-specific screening.

Gynecological Evaluation

Perform at baseline and annually and as indicated for ongoing problems. This examination should include direct visualization of the vulva, vagina, and cervix, and a bimanual pelvic examination that includes a digital rectal examination.

Cytologic Screening

Cervical Pap tests: Perform at baseline and then 6 months after baseline; repeat annually, as long as results are normal

  • Abnormal Pap tests results should be repeated every 3 to 6 months until two successive normal Pap tests are reported
  • Colposcopy should be performed for women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis. Women with cervical HSIL should be referred for high-resolution anoscopy.

Anal Pap tests: Perform at baseline and annually for women with a history of anogenital condyloma or abnormal cervical/vulvar histology

Post-hysterectomy cervical screening: Perform an annual cervical Pap test when:

  • Hysterectomy was performed because of high-grade dysplasia, HPV-related anogenital dysplasia of the cervix, or carcinoma
  • A supracervical hysterectomy (uterus removed and cervix left in place) was performed
  • The reason for the hysterectomy cannot be determined by patient self-report or other means
  • Any cervical tissue remains
  • Annual Pap tests are not recommended for HIV-infected women who have undergone a total hysterectomy for reasons not related to cervical abnormalities.

STI Screening 

RPR or VDRL for syphilis with verification of positive test by confirmatory FTA-Abs or TP-PA: Perform at baseline and at least annually; every 3 months for patients with ongoing high-risk behavior

Gonorrhea and chlamydia: Perform at baseline and at least annually for women with one of the following: recent STI, multiple sexual partners, a new sexual partner, or a sexual partner with symptoms of an STI.

All sites of exposure are screened. 

Mammography

Annual screening should begin at age 40; however, the optimal age of initiation for breast screening and the intervals for mammography are still being studied [American Cancer Society].

Bone Mineral Densities 

Baseline screening should occur at menopause and after 50. The frequency thereafter has not been determined [National Osteoporosis Foundation].

Immunizations

See: Recommended Immunizations for Non-Pregnant HIV-Infected Adults

 

Antiretroviral Therapy

May 2009

RECOMMENDATION

Benefits of ART

Initiating treatment with ART at appropriate CD4 counts and viral load thresholds may be especially important in HIV-infected people over the age of 50 because there is evidence that they progress more quickly and have a lower potential for immune restoration [1,2]. Appropriate treatment with ART may mitigate some negative effects of aging with HIV infection, such as cognitive decline [3].

Risks of ART

Risks of initiating ART include metabolic complications, such as lipid disorders, insulin resistance and diabetes, altered body fat distribution, and, consequently, a higher risk of cardiovascular disease. These ARV-related complications can be difficult to diagnose and manage in older patients who may have the same, age-related, pre-existent metabolic abnormalities.

Another potential risk of ART includes bone loss, although the relationship among HIV infection, ARV therapy, and bone loss in women remains unclear [4,5]. Components of ART, in particular NRTIs and PIs, have been associated with a decrease in bone density. However, some evidence does exist for higher bone density in women exposed to nevirapine [6]. Multiple factors contribute to the development of osteopenia/osteoporosis in HIV-infected women, including age, heredity, and HIV infection itself.

Adverse Drug Reactions and Drug-Drug Interactions

RECOMMENDATION
  • Clinicians should assess for signs or symptoms of adverse reactions, drug-drug interactions, and cumulative side effects when patients are receiving multiple types or classes of medications for comorbidities and/or HIV.

The risk for drug interactions and/or serious toxicities increases with the number of medications a patient is taking, the age of the patient, the severity of the disease being treated, and the presence of renal and hepatic dysfunction. Older HIV-infected women frequently will have all of these risk factors and will be at increased risk for iatrogenic harm. Older people may have altered metabolism, which can impact pharmacokinetics and contribute to ARV toxicities and drug interactions.

Drug interactions with ART, particularly PIs, have become an increasingly complex challenge for clinicians treating HIV-infected patients. HAART medications are known to interact with major classes of drugs that are commonly used to treat older patients, such as antidepressants, anticonvulsants, lipid-lowering agents, and many antibiotics and antifungals. Clinicians need to be aware of drugs that are associated with clinically significant drug interactions with HAART in order to avoid the use of these drugs or to monitor patients for virologic failure or toxicity.

References:
  1. Lederman MM, McKinnis R, Kelleher D, et al. Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: Age inversely predicts naive CD4 cell count increase. AIDS 2000;14:2635-2642.
  2. Belanger F, Meyer L, Carre N, et al. Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: The SEROCO cohort (1988-1994). The Seroco Study Group. Int J Epidemiol 1997;26:1340-1345.
  3. Vance DE, Burrage JW. Promoting successful cognitive aging in adults with HIV: strategies for intervention. J Gerontol Nurs 2006;32:34-41.
  4. Glesby MJ. Bone disorders in human immunodeficiency virus infection. Clin Infect Dis 2003;37(Suppl):S91-S95. Review.
  5. Dolan SE, Huang JS, Killilea KM, et al. Reduced bone density in HIV-infected women. AIDS 2004;18:475-483.
  6. Anastos K, et al. The association of bone mineral density with HIV infection and antiretroviral treatment in women. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, Abstract 744, 2004.

Hormone Replacement Therapy

May 2009

RECOMMENDATIONS
  • Clinicians should refer HIV-infected women experiencing severe symptoms of menopause to a clinician experienced in the most current management of menopausal symptoms. An individualized risk/benefit analysis of the use of HRT should be performed regardless of whether or not the woman is receiving ART.
  • Clinicians should discuss with HIV-infected women the benefits of exercise, weight control, improved nutrition, including calcium supplementation, and smoking cessation for the prevention of osteoporosis and coronary heart disease.

Menopause occurs at different ages for women. In general, women undergo menopause between the ages of 40 and 50. Signs and symptoms of menopause before the age of 40 is considered premature menopause.

HRT is no longer the standard of care for relief of menopausal symptoms. Recent studies have shown limited benefit for the prevention of cardiovascular risk. Therefore, if used, HRT should be used at the lowest effective doses for the shortest time possible for relief of menopausal symptoms [1].

Guidelines for HRT

Prescribing HRT:

  • Provide HRT for the shortest possible time at the lowest effective doses
  • Consult with the patient at least once a year about HRT therapy, working toward successfully discontinuing the use of HRT
  • Recommend regular breast cancer screening: Annual clinical breast examinations and annual mammogram for women >40 (the optimal age of initiation for breast screening and the intervals for mammography are still being studied).

Clinicians can also refer to the following organizations for updated guidelines:

Alternatives to HRT

Safe and well-established alternatives to HRT are available for the prevention of coronary heart disease and osteoporosis. In addition, alternatives to HRT are available for treatment of symptoms of menopause (see below) but have not been shown to be as effective as HRT. Clinicians should remind women of the protective effects of exercise; weight control; improved nutrition, including calcium supplementation; and smoking cessation.

Alternatives to HRT for specific signs or symptoms of menopause:

  • Hot flashes [2,3]/menopause symptom alleviation: Paroxetine, gabapentin, clonidine
  • Vaginal dryness/atrophy: Water-based lubricants and vaginal estrogen preparations
  • Prevention or treatment of osteoporosis: 
    • Alendronate sodium, risendronate, raloxifene, calcitonin
    • Smoking cessation
    • Decreased alcohol consumption
    • Increased physical activity
    • Calcium and vitamin D supplementation and correction of malnutrition

HRT Interactions with ART

RECOMMENDATION
  • Because amprenavir and fosamprenavir levels are reduced with ethinyl estradiol and norethindrone use, they should not be used with hormone replacement therapy.

No significant interactions between HRT and HAART have been documented. However, studies of combined hormonal oral contraceptives show a 20% decrease in amprenavir (and presumably fosamprenavir) levels. Data also show that some ARV drugs reduce the AUC for estradiol in oral contraceptives. However, there is no current recommendation to increase the doses of estrogen in HRT while receiving HAART. In addition, risks for cardiovascular disease and the questionable benefit of HRT in decreasing osteoporosis in menopause have limited the use of HRT in all women.

References:
  1. The North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007;14:168-182.
  2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071.
  3. Tice JA, Grady D. Alternatives to estrogen for treatment of hot flashes: are they effective and safe? JAMA 2006;295:2076-2078.

Mental Health and Substance Abuse

May 2009

RECOMMENDATIONS
  • Clinicians should perform a mental health assessment at baseline and at least annually. The assessment should include the following components (I):
  • Cognitive impairment, depression, anxiety, posttraumatic stress disorder, suicidal/violent ideation, and alcohol and substance use
    • Sleep habits and appetite assessment
    • Psychiatric history, including psychotropic medications
    • Psychosocial assessment, including domestic violence, housing status, and presence of social support
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (II)
  • Clinicians should incorporate selected brief screening instruments in the patient assessment. These instruments should be tailored for optimal use at initial, annual, and interim visits. The chosen screening instruments should be adjusted for the patient’s mental health or substance use history.
KEY POINT
  • Depressive symptoms and negative life events have been associated with symptoms of menopause in HIV-infected women.

Depression affects as many as 20% of the HIV-infected population [1], and stress and depression have been reported among older women with HIV infection. Many of these women experience increased stress from limited healthcare services, lack of resources, and caring for others as well as themselves. In addition, older women are often omitted from research and educational programs. Mental health interventions, including the use of antidepressants, may provide a quality-of-life benefit for HIV-infected women who suffer from depressive symptoms [2].

Unmet needs for mental health services, substance use treatment, and social services may inhibit effective adherence and treatment for HIV [3]. For some patients, referrals for these services may be necessary. For additional information, see NYSDOH AIDS Institute guidelines on mental health and substance use.

References:
  1. Komiti A, Judd F, Grech P, et al. Depression in people living with HIV/AIDS attending primary care and outpatient clinics. Aust N Z J Psychiatry 2003;37:70-77.
  2. Miller SA, Santoro N, Lo Y, et al. Menopause symptoms in HIV-infected and drug-using women. Menopause 2005;12:348-356.
  3. Cook JA, Grey D, Burke J, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am J Public Health 2004;94:1133-1140.

Sexual Dysfunction

May 2009

RECOMMENDATION
  • Clinicians should assess older HIV-infected women for sexual dysfunction and/or decreased libido; testosterone supplementation should not be used for treating these conditions.

Clinicians caring for HIV-infected older women have noted that decreased libido is a common complaint affecting quality of life. The lack of clinical trials on effective therapy for women has meant that clinicians are addressing a complicated issue with little scientific guidance. There are no data supporting the efficacy of testosterone use for the management of sexual dysfunction or decreased libido associated with menopause and/or HIV. Because the side effects, safety, and efficacy of long-term use of testosterone currently are not known, testosterone supplementation is not advised. However, decreased libido caused by depression or other psychosocial stressors should be considered and may be treatable.

All Recommendations

Women with HIV Infection Guidelines Committee, May 2009

ALL RECOMMENDATIONS: MEDICAL CARE FOR MENOPAUSAL AND OLDER WOMEN
Identification and Prevention of HIV Infection
  • Clinicians should discuss sexual and other risk behaviors and HIV prevention education at routine clinical visits for all HIV-infected women, regardless of age.
  • Clinicians should consider acute retroviral syndrome in the differential diagnosis for older women who present with flu-like illnesses.
Antiretroviral Therapy 
  • Clinicians should follow standard guidelines for initiation of ART in older women.
  • Clinicians should assess for signs or symptoms of adverse reactions, drug-drug interactions, and cumulative side effects when patients are receiving multiple types or classes of medications for comorbidities and/or HIV.
Hormone Replacement Therapy 
  • Clinicians should refer HIV-infected women experiencing severe symptoms of menopause to a clinician experienced in the most current management of menopausal symptoms. An individualized risk/benefit analysis of the use of HRT should be performed regardless of whether or not the woman is receiving ART.
  • Clinicians should discuss with HIV-infected women the benefits of exercise, weight control, improved nutrition, including calcium supplementation, and smoking cessation for the prevention of osteoporosis and coronary heart disease.
  • Because amprenavir and fosamprenavir levels are reduced with ethinyl estradiol and norethindrone use, they should not be used with hormone replacement therapy.
Mental Health and Substance Abuse 
  • Clinicians should perform a mental health assessment at baseline and at least annually. The assessment should include the following components (I):
    • Cognitive impairment, depression, anxiety, posttraumatic stress disorder, suicidal/violent ideation, and alcohol and substance use
    • Sleep habits and appetite assessment
    • Psychiatric history, including psychotropic medications
    • Psychosocial assessment, including domestic violence, housing status, and presence of social support
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (II)
  • Clinicians should incorporate selected brief screening instruments in the patient assessment. These instruments should be tailored for optimal use at initial, annual, and interim visits. The chosen screening instruments should be adjusted for the patient’s mental health or substance use history.
Sexual Dysfunction 
  • Clinicians should assess older HIV-infected women for sexual dysfunction and/or decreased libido; testosterone supplementation should not be used for treating these conditions.

HIV-2 Guideline

Introduction

Medical Care Criteria Committee, April 2012

HIV-2 was first described in 1985 [1] and was isolated in 1986 in West Africa [2], where it is currently endemic. The Centers for Disease Control and Prevention (CDC) reported that, from 1988 to June 2010, 166 cases had met the CDC case definition of HIV-2 infection in the United States [3]. The largest number of cases were from the Northeast, including 77 from New York City [3]. The majority of cases had a West African origin or connection [3]. However, a report from New York City suggests that HIV-2 may be underreported because antibody cross-reactivity between HIV-1 and HIV-2 is common and frequently results in misdiagnosis of HIV-2 as HIV-1 or dual infection [4]. Incorporating a type-differentiating immunoassay into the HIV screening protocol can assist in identifying the type [4].

HIV-2 is associated with lower viral load levels and slower rates of CD4 decline and clinical progression compared with HIV-1 [5,6]; 86% to 95% of people infected with HIV-2 are long-term nonprogressors [7,8]. Recent data show that survival of persons with undetectable HIV-2 viral load is similar to that of the general population [8]. However, HIV-2 can cause immunosuppression, as well as AIDS characterized by the same signs, symptoms, and opportunistic infections that are seen in HIV-1. HIV-2-associated AIDS may often be associated with lower viral load levels than HIV-1 (>10,000 copies/mL in HIV-2 versus sometimes millions of copies/mL in HIV-1) [8].

In contrast to the detailed knowledge base for the management of HIV-1, no clinical trials have been conducted to date to guide decision-making in the management of HIV-2-related immunosuppression and progression of disease. Studies of virologic and immunologic responses to antiretroviral therapy (ART) have demonstrated a higher CD4 cell increase in HIV-1-infected patients compared with HIV-2-infected patients after initiation of therapy [9-11]. These factors, combined with the absence of controlled trials of ART for HIV-2, contribute to the challenge of optimal treatment of HIV-2.

KEY POINTS
  • HIV-2-infected individuals with progressive disease are less likely to respond as predictably to ART as patients with HIV-1 infection.
  • The choice of ART for HIV-2 differs from that for HIV-1, underscoring the importance of differentiating between HIV-1 and HIV-2 in patients at risk for HIV-2 infection.
  • Clinical monitoring of HIV-2 is hampered by the absence of assays with Food and Drug Administration (FDA) approval for quantification of HIV-2 viral load, as well as a lack of consensus on interpretation of HIV-2 resistance testing.
References:
  1. Barin F, M’Boup S, Denis F, et al. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of West Africa. Lancet 1985;2:1387-1389. [PubMed]
  2. Clavel F, Guetard D, Brun-Vezinet F, et al. Isolation of a new human retrovirus from West African patients with AIDS. Science 1986;233:343-346. [PubMed]
  3. Centers for Disease Control and Prevention (CDC). HIV-2 Infection Surveillance — United States, 1987-2009. MMWR Morb Mortal Wkly Rep2011;60:985-988. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6029a3.htm
  4. Torian LV, Eavey JJ, Punsalang AP, et al. HIV type 2 in New York City, 2000-2008. Clin Infect Dis 2010;51:1334-1342. [PubMed]
  5. Andersson S, Norrgren H, DaSilva Z, et al. Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: Significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infections. Arch Intern Med 2000;160:3286-3293. [PubMed]
  6. Marlink R, Kani P, Thior I, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994;265:1587-1590. [PubMed]
  7. De Silva TI, Cotten M, Rowland-Jones SL. HIV-2: The forgotten AIDS virus. Trends Microbiol 2008;16:588-595. [PubMed]
  8. van der Loeff MF, Larke N, Kaye S, et al. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village. Retrovirology 2010;7:46. [PubMed]
  9. Drylewicz J, Matheron S, Lazaro E, et al. Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France. AIDS 2008;22:457-468. [PubMed]
  10. Jallow S, Alabi A, Sarge-Njie R, et al. Virological response to highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 2 (HIV-2) and in patients dually infected with HIV-1 and HIV-2 in the Gambia and emergence of drug-resistant variants. J Clin Microbiol 2009;47:2200-2208. [PubMed]
  11. Matheron S, Damond F, Benard A, et al. CD4 cell recovery in treated HIV-2-infected adults is lower than expected: Results from the French ANRS CO5 HIV-2 cohort. AIDS 2006;20:459-462. [PubMed]

 

Natural History and Epidemiology

Medical Care Criteria Committee, April 2012

HIV-2 Mono-Infection

HIV-1 and HIV-2 are closely related retroviruses of the same genus (Lentiviridae) and share the same modes of transmission. Both types are considered to have arisen from the introduction of simian immunodeficiency virus into the human population, although they derive from different primate simian immunodeficiency viruses: HIV-2 from SIVsm (sooty mangabey) and HIV-1 from SIVcpz (chimpanzee).

HIV-2 is present throughout West Africa, with the highest prevalence in its area of origin, Guinea-Bissau, where in 1990, 8% of adults and 20% of persons over 40 years of age were infected [1,2]. HIV-2 has been reported in Portugal and France, as well as countries with colonial ties to these nations (Angola, Mozambique, Brazil, and parts of India), due to large West African immigrant populations and/or long histories of commerce and other ties to West Africa.

HIV-1/HIV-2 Co-Infection

HIV-1/HIV-2 co-infection in West Africa is increasing, particularly in border countries between West and East Africa [2]. In the United States, co-infection has also been reported. Among the 166 cases of HIV-2 reported by the CDC, 19 patients (11%) tested positive for possible HIV-1/HIV-2 co-infection. However, the extent of HIV-1/HIV-2 co-infection within the entire patient population could not be assessed due to incomplete HIV-1 testing results for some individuals [3].

The dynamics of interaction between HIV-1 and HIV-2 have been a matter of controversy for decades [4-7], and expertise in the area of HIV-1/HIV-2 co-infection remains limited. One study suggested that mortality rates were higher among HIV-1/HIV-2 co-infected individuals than HIV-1 mono-infected individuals [7], but this may be dependent on which infection occurred first. Over time, HIV-1 seems to out-compete HIV-2 as the primary virus behind disease progression in HIV-1/HIV-2 co-infected persons. Data also suggest that the mortality associated with HIV-1/HIV-2 co-infection is dependent on CD4 count and is higher than in HIV-2 mono-infected individuals matched for disease stage [8].

HIV-1/HIV-2 co-infection is difficult to diagnose due to the cross-reactivity of antibodies, as well as viral antigens, making treatment decisions based on co-infection difficult to determine. Genetic sequence verification of both viral sequences should be encouraged for diagnosis of HIV-1/HIV-2 co-infection. See HIV-2 > Screening and Diagnosis for guidance on the tests that are best designed to differentiate between HIV-1 and HIV-2.

References:
  1. Lemey P, Pybus OG, Wang B, et al. Tracing the origin and history of the HIV-2 epidemic. Proc Natl Acad Sci USA 2003;100:6588-6592. [PubMed]
  2. De Silva TI, van Tienen C, Rowland-Jones SL, et al. Dual infection with HIV-1 and HIV-2: Double trouble or destructive interference? HIV Ther 2010;4:305-323. [PubMed]
  3. Centers for Disease Control and Prevention (CDC). HIV-2 Infection Surveillance — United States, 1987-2009. MMWR Morb Mortal Wkly Rep2011;60:985-988. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6029a3.htm
  4. Greenberg AE, Wiktor SZ, Decock KM, et al. HIV-2 and natural protection against HIV-1 infection. Science 1996;272:1959a. [PubMed]
  5. Nkengasong JN, Kestens L, Ghys PD, et al. Dual infection with human immunodeficiency virus type 1 and type 2: Impact on HIV type 1 viral load and immune activation markers in HIV-seropositive female sex workers in Abidjan, Ivory Coast. AIDS Res Hum Retroviruses 2000;16:1371-1378. [PubMed]
  6. Koblavi-Dème S, Kestens L, Hanson D, et al. Differences in HIV-2 plasma viral load and immune activation in HIV-1 and HIV-2 dually infected persons and those infected with HIV-2 only in Abidjan, Côte D’Ivoire. AIDS 2004;18:413-419. [PubMed]
  7. Holmgren B, da Silva Z, Vastrup P, et al. Mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in a middle-aged and older population in Guinea-Bissau. Retrovirology 2007;4:85. [PubMed]
  8. Alabi AS, Jaffar S, Ariyoshi K, et al. Plasma viral load, CD4 cell percentage, HLA and survival of HIV-1, HIV-2, and dually infected Gambian patients. AIDS 2003;17:1513-1520. [PubMed]

Screening and Diagnosis

Medical Care Criteria Committee, April 2012

RECOMMENDATIONS
  • Specimens submitted for HIV testing should be screened by an enzyme immunoassay (EIA) that detects HIV-1, HIV-1 group O, and HIV-2. All laboratories performing HIV diagnostic testing should incorporate algorithms for differentiation of HIV-1 versus HIV-2 in repeatedly reactive samples. (AIII)
  • When HIV-1/HIV-2 combination screening yields a reactive result but is followed by indeterminate or nonreactive HIV-1 Western blot, clinicians should:
    • Obtain a plasma HIV RNA assay to exclude acute HIV-1 infection (AIII)
    • Obtain testing for HIV-2 antibodies with an FDA-approved HIV-1/HIV-2 type-differentiating immunoassay if acute HIV-1 infection has been excluded (AIII)
    • Consider specimens positive for HIV-2 if they are repeatedly reactive on an HIV-1/HIV-2 screening test and reactive for HIV-2 antibodies on the HIV-1/HIV-2 differentiation test (AIII)
  • Clinicians should use HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols when screening for HIV in patients who meet the criteria outlined below. (AIII)

All New York State public health laboratories and all major commercial laboratories now perform combination screening for antibodies to HIV-1 group M, HIV-1 group O, and HIV-2. Most of the FDA-approved, Clinical Laboratory Improvement Amendment (CLIA)-waived HIV rapid tests also detect HIV-1 and HIV-2 antibodies. For additional information regarding HIV-1/HIV-2 combination rapid tests, see HIV Testing: Characteristics of FDA-Approved Rapid HIV Tests.

When an HIV-1/HIV-2 combination screening test yields a reactive result and an HIV-1 Western blot yields an indeterminate or nonreactive result, additional testing is indicated. Because the current tests used to screen for HIV infection are more sensitive than the Western blot, a negative or indeterminate HIV-1 Western blot could signify early HIV-1 infection or HIV-2 infection; an HIV-1 RNA assay should be performed to diagnose or exclude early HIV-1 infection. If early HIV-1 infection has been excluded, then HIV-2 antibody testing should be performed with an FDA-approved HIV-1/HIV-2 type-differentiating immunoassay.

Click to enlarge
Figure 1: Click to enlarge

A limited number of laboratories offer an HIV-2 Western blot test, none of which has FDA approval, and interpretation is complicated due to significant cross-reactivity between HIV-1 and HIV-2 antibodies.

An alternative HIV diagnostic algorithm has been proposed in which an FDA-approved HIV-1/HIV-2 immunoassay that differentiates between HIV-1 and HIV-2 antibodies is used as a supplemental test instead of an HIV-1 or HIV-2 Western blot (see Figure 1). According to this algorithm, a sample that is repeatedly reactive on an HIV-1/HIV-2 screening test and reactive for only HIV-2 antibodies on an HIV-1/HIV-2 differentiating immunoassay is considered to be positive for HIV-2 infection. An HIV-2 RNA or DNA detection test may be obtained in addition to serology for further confirmation. In cases where HIV-1 or HIV-2 antibodies are not detected by the HIV-1/HIV-2 type-differentiating immunoassay, the alternative diagnostic algorithm indicates that a plasma HIV-1 RNA assay should be performed to diagnose or exclude early HIV-1 infection.

KEY POINT
  • Diagnostic HIV laboratory tests and interpretation algorithms evolve; individual laboratories have internal protocols for reporting tests with preliminary results. Indeterminate, inconclusive, non-diagnostic, and pending validation are among the terms used when preliminary results cannot be classified definitively. The clinician should contact the appropriate laboratory authority to determine the significance of the non-definitive results and the supplemental testing that would be indicated. This is of particular importance in tests from patients with suspected HIV-2 infection. Clinicians should become familiar with the internal test-reporting policies of their institutions.

Populations for whom HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols should be included when screening for HIV are listed below.

Clinicians should be alert to the possibility of HIV-2 infection in patients who:

  • Originated in or have traveled to an HIV-2-endemic area
  • Received medical care, injections, immunizations, phlebotomy, surgery, or blood products or participated in vaccine trials in an HIV-2-endemic area*
  • Had sexual or needle-sharing contact with persons who are infected with HIV-2 or are from an HIV-2-endemic area*
  • Were born to a mother with HIV-2 infection (see Testing and Prophylaxis for HIV-2-Exposed Infants)
  • Had opportunistic infections or other clinical symptoms of HIV/AIDS but tested negative or indeterminate for HIV-1
  • Received multiple HIV-1 indeterminate antibody test results
  • Have a confirmed diagnosis of HIV-1 but an undetectable viral load that is incompatible with the clinical or immunological status

*Endemic areas include: West African countries (Guinea-Bissau, Cape Verde, Ivory Coast, Gambia, Mali, Mauritania, Nigeria, Sierra Leone, Benin, Burkina Faso, Ghana, Guinea, Liberia, Niger, Sao Tome, Senegal, and Togo), as well as Angola, Mozambique, and India.

For more information regarding HIV-2 testing, contact one of the public health laboratories:

  • Care providers in New York City: Contact the New York City Department of Health and Mental Hygiene (NYC DOHMH) at 212-447-2864 for assistance with HIV-2 diagnostic testing
  • Care providers in New York State, who are outside of New York City: Contact the New York State Department of Health (NYSDOH) Wadsworth Center Laboratory at 518-474-2163 for assistance with HIV-2 diagnostic testing
Reference:
  1. Centers for Disease Control and Prevention (CDC). DRAFT Recommendations: Diagnostic Laboratory Testing for HIV Infection in the United States. Presented at the 2012 HIV Diagnostics Conference Feedback Session held on December 14, 2012. CDC: Atlanta; 2012. Available at: www.cdc.gov/hiv/testing/lab/guidelines/index.html

Monitoring

April 2012

RECOMMENDATION
  • Clinicians should monitor HIV-2-infected patients by clinical evaluation and CD4 cell count. (BIII)

CD4 count is the most readily available means for monitoring disease progression in HIV-2-infected patients. However, CD4 counts often will not increase as dramatically as generally occurs with successful therapy of HIV-1 mono-infection [1]. Commercially available HIV-1 viral load tests do not detect or quantify HIV-2, and currently there is no FDA-approved viral load test for HIV-2. In the U.S, two laboratories have developed and validated HIV-2 viral load tests for clinical use according to Clinical Laboratory Improvement Amendments (CLIA) requirements. Health care providers located in New York State or who provide care for New York State residents should contact the Bloodborne Viruses Laboratory at the Wadsworth Center, New York State Department of Health (NYSDOH) at 518-474-2163.

The Wadsworth Center Laboratory holds a New York State clinical laboratory permit and its HIV-2 viral load test has been approved by the NYSDOH Clinical Laboratory Evaluation Program, as required under New York State Public Health Law. HIV-2 viral load testing is performed free of charge at the Wadsworth Center, but testing is restricted to New York State residents. For HIV-2 viral load testing of patients from states other than New York, health care providers should contact the Clinical Retrovirus Laboratory at the University of Washington at 206-897-5210. The University of Washington’s HIV-2 viral load test is conducted in a CLIA-certified and College of American Pathologists (CAP)-accredited laboratory.

Reference:
  1. Matheron S, Damond F, Benard A, et al. CD4 cell recovery in treated HIV-2-infected adults is lower than expected: Results from the French ANRS CO5 HIV-2 cohort. AIDS 2006;20:459-462. [PubMed]

Treatment

April 2012

RECOMMENDATIONS
  • Clinicians should include two NRTIs and an appropriate boosted PI, such as lopinavir, saquinavir, or darunavir, when prescribing ART for HIV-2 mono-infected or HIV-1/HIV-2 co-infected individuals (see text). (AIII)
  • Clinicians should not prescribe NNRTIs or the PIs nelfinavir, atazanavir, or fosamprenavir as part of an ART regimen against HIV-2 mono-infection; these agents may be used as part of a regimen for HIV-1/HIV-2 co-infected patients if adequate treatment for HIV-2 is also included [20]. (BIII)
  • Clinicians should consult with a provider with experience in the management of HIV-2 before initiating ART in HIV-2-infected patients. (AIII)
  • Clinicians should educate patients with confirmed HIV-2 infection about the lack of data regarding treatment of HIV-2 and should review individual benefits and risks of initiating treatment. Patients should make the final decision of whether and when to initiate ART.

No randomized clinical trials have been conducted to determine when to initiate ART in the setting of HIV-2 infection, and the best choices of therapy for HIV-2 infection remain under study. Because the optimal treatment strategy for HIV-2 infection has not been defined, the recommendations provided in this section are based on this committee’s expert opinion.

Although HIV-2 is generally less aggressive, and progression to AIDS is less frequent, HIV-2 responds less predictably to ART when progression occurs, and response is more difficult to monitor (see below for available data regarding HIV-2 response to ART). The standard methods and interpretation protocols that are used to monitor ART for HIV-1-infected patients may not apply for HIV-2-infected patients. Some ART regimens that are appropriate for HIV-1 infection may not be as effective for HIV-2. The following factors should be considered when deciding whether or not to initiate ART in HIV-2-infected patients:

  • The majority of HIV-2-infected patients are long-term nonprogressors
  • HIV-2 may confer more rapid resistance to ART agents due to wild-type genetic sequence that results in a significant increase in resistance to ART agents compared with HIV-1 [2-4]
  • Pathways for the development of drug mutations may differ between the two viruses
  • Recent data have shown a significant reduction in HIV-1 transmission risk between serodiscordant heterosexual couples when the positive partner was receiving ART [5]; lower viral load level may also reduce HIV-2 transmission risk
KEY POINT
  • Few data exist for the diagnosis and management of HIV-1/HIV-2 co-infection; however, clinical management currently focuses on controlling HIV-1 infection with agents that are active against both HIV-1 and HIV-2.

Efficacy of ART Against HIV-2 Infection

Nucleoside reverse transcriptase inhibitors (NRTIs): 

  • Although most in vitro studies have shown that similar concentrations of NRTIs are needed to block both HIV-1 and HIV-2 replication, data suggest that some NRTIs may not be as effective against HIV-2 [6]. For example, HIV-1 more readily incorporates zidovudine and is more susceptible to zidovudine than HIV-2, and there is a lower barrier to resistance with HIV-2 than with HIV-1 [2,7].
  • Genotypic analysis of HIV-2-infected patients on ART has shown that many of the same amino acid substitutions that are associated with NRTI resistance in HIV-1 may be implicated in HIV-2. Some resistance mutations (K65R, Q151M, and M184V) in combination can confer class-wide NRTI resistance and cause rapid virologic failure [2].

Non-nucleoside reverse transcriptase inhibitors (NNRTIs): 

  • NNRTIs block HIV-1 reverse transcription through a specific binding site that is not present in HIV-2; this class of drugs will not be effective against HIV-2 [8,9].
  • HIV-2 appears to be intrinsically resistant to NNRTIs [8]; the Y188L polymorphism appears naturally in all HIV-2 isolates. Reversion to Y188 restores the reverse transcriptase sensitivity to some NNRTIs, including efavirenz and delavirdine [10].
  • In general, NNRTIs inhibit HIV-2 at effective concentrations that are at least 50-fold higher than those that inhibit HIV-1 [11], making the use of these drugs for HIV-2 infection problematic.
  • Etravirine appears to have limited activity against HIV-2, but this may not be clinically relevant because the mean 50% effective concentration in MT4 cells is 2500-fold higher than that observed for HIV-1 [12].

Protease inhibitors (PIs): 

  • PIs appear to have variable activity and accelerated genotypic resistance [4].
  • HIV-2 expresses natural polymorphisms in the protease that may be implicated in emergent drug resistance and accelerate time to development of PI resistance [4].
  • One study noted that the pathways for HIV-2 protease drug resistance may differ from those for HIV-1 [6].
  • Saquinavir, lopinavir, and darunavir have shown comparable activity against HIV-1 and HIV-2 [13-15].
  • Indinavir, nelfinavir, and ritonavir may be less active against HIV-2 than HIV-1.
  • Atazanavir has lower and variable activity against HIV-2 in comparison with HIV-1 [14].
  • The data regarding tipranavir are conflicting.
  • Some natural polymorphisms in HIV-2 may confer baseline resistance to fosamprenavir.

Integrase strand transfer inhibitors (INSTIs): 

  • Little is known about the use of INSTIs in HIV-2 infection.
  • The INSTIs raltegravir and elvitegravir have demonstrated activity in vitro [16]. Clinical response to raltegravir was reported in a patient with highly treatment-experienced HIV-2 infection [17], but the emergence of mutations was reported in another patient [18].

CCR5 co-receptor antagonists:

  • The activity of maraviroc has been limited to patients with CCR5-tropic viruses.
  • Primary HIV-2 isolates can utilize a broad range of co-receptors, including CXCR4, CCR5, CCT-5, GPR15, and CXCR6. This limits the therapeutic utility of maraviroc in HIV-2 infection.

Fusion inhibitors: HIV-2 is intrinsically resistant to the fusion inhibitor enfuvirtide [11,19].

As with disease monitoring, monitoring of response to treatment for HIV-2 is more challenging than for HIV-1. Viral load and ART resistance assays for HIV-2 are not commercially available. However, such tests may be available under research Investigational New Drug (IND) protocols. Results generated by these assays should be interpreted with caution due to the IND classification and the absence of standardized interpretation protocols [20]. An HIV-2 viral load assay developed by NYSDOH Wadsworth Center is currently undergoing validation for clinical use. Contact the laboratory regarding availability at 518-474-2163.

References:
  1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2011:1-174. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
  2. Smith RA, Anderson DJ, Pyrak CL, et al. Antiretroviral drug resistance in HIV-2: Three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis 2009;199:1323-1326. [PubMed]
  3. Rodés B, Sheldon J, Toro C, et al. Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing antiretroviral therapy. J Antimicrob Chemother 2006;57:709-713. [PubMed]
  4. Ntemgwa M, Brenner BG, Oliveira M, et al. Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Antimicrob Agents Chemother 2007;51:604-610. [PubMed]
  5. Cohen MS, Chen YQ, McCauley M, et al.; HPTN 052 Study Team. Prevention of HIV-infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505. [PubMed]
  6. Ntemgwa ML, d’Aquin Toni T, Brenner BG, et al. Antiretroviral drug resistance in human immunodeficiency virus type 2. Antimicrob Agents Chemother 2009;53:3611-3619. [PubMed]
  7. Boyer PL, Sarafianos SG, Clark PK, et al. Why do HIV-1 and HIV-2 use different pathways to develop AZT resistance? PLoS Pathog 2006;2:e10. [PubMed]
  8. Tuaillon E, Gueudin M, Lemee V, et al. Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups. J Acquired Immune Defic Syndr 2004;37: 1543-1549. [PubMed]
  9. Ren J, Bird LE, Chamberlain PP, et al. Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors. Proc Natl Acad Sci USA 2002;99:14410-14415. [PubMed]
  10. Isaka Y, Miki S, Kawauchi S, et al. A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors. Arch Virol 2001;146:743-755. [PubMed]
  11. Witvrouw M, Pannecouque C, Switzer WM, et al. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: Implications for treatment and postexposure prophylaxis. Antivir Ther 2004;9:57-65. [PubMed]
  12. Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2004;48:4680-4686. [PubMed]
  13. Benard A, Damond F, Campa P, et al. Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naïve HIV-2-infected patients. AIDS 2009;23:1171-1179. [PubMed]
  14. Desbois D, Roquebert B, Peytavin G, et al. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother 2008;52:1545-1548. [PubMed]
  15. Brower ET, Bacha UM, Kawasaki Y, et al. Inhibition of HIV-2 protease by HIV-1 protease inhibitors in clinical use. Chem Biol Drug Des2008;71:298-305. [PubMed]
  16. Roquebert B, Damond F, Collin G, et al. HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother 2008;62:914-920. [PubMed]
  17. Garrett N, Xu L, Smit E, et al. Raltegravir treatment response in an HIV-2 infected patient: A case report. AIDS 2008;22:1091-1098. [PubMed]
  18. Xu L, Anderson J, Garrett N, et al. Dynamics of raltegravir resistance profile in an HIV type 2-infected patient. AIDS Res Hum Retroviruses 2009;25:843-847. [PubMed]
  19. Poveda E, Rodes B, Toro C, et al. Are fusion inhibitors active against all HIV variants? AIDS Res Hum Retroviruses 2004;20:347-348. [PubMed]
  20. Matheron S, Damond F, Benard A, et al. CD4 cell recovery in treated HIV-2-infected adults is lower than expected: Results from the French ANRS CO5 HIV-2 cohort. AIDS 2006;20:459-462. [PubMed]

Pregnancy

April 2012

RECOMMENDATION
  • Clinicians caring for pregnant patients with suspected or diagnosed HIV-2 should consult with a provider with experience in HIV-2 testing and management, including perinatal ART for HIV-2-infected pregnant women and postnatal ART for HIV-2-exposed infants. (AIII)

HIV-2 Testing for Women during Pregnancy and Delivery

RECOMMENDATION
  • Clinicians should use HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols when screening for HIV in pregnant women who meet the criteria outlined in the text. (AIII)

HIV testing during pregnancy should be performed using a screening test that detects HIV-1 and HIV-2 antibodies. For pregnant women who meet the criteria outlined previously, HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols should be used. In New York State, if a woman presents for delivery without documentation of a negative HIV test during the current pregnancy and is not known to have HIV infection, the mother must receive expedited HIV testing with her consent; if she declines, the newborn must receive testing with or without maternal consent. For more information regarding HIV testing during pregnancy, refer to HIV Testing During Pregnancy and at Delivery Guideline.

HIV-2 Treatment and Prophylaxis during Pregnancy

RECOMMENDATIONS
  • Zidovudine plus lamivudine with lopinavir/ritonavir is the currently recommended regimen for HIV-2-infected pregnant women. (AIII)
  • For HIV-2-infected women who decline ART or who are unable to adhere to an ART regimen during pregnancy, single-drug prophylaxis with zidovudine during pregnancy and intrapartum should be used as an alternative for preventing HIV-2 mother-to-child transmission. (BIII)

The risk of mother-to-child transmission (MTCT) of HIV-2 is significantly lower than that of HIV-1 [1,2]. However, high HIV-2 viral load levels may be associated with increased risk for MTCT. In one study, MTCT of HIV-2 occurred more frequently in the setting of high maternal viral load levels (>10,000 copies/mL) [3]. Advanced HIV-2 disease has also been associated with HIV-2 MTCT [4], as has early HIV-2 infection during pregnancy [1]. These findings suggest that ART for HIV-2, regardless of the clinical or immunological status of the patient, may be indicated during pregnancy, similar to the practice for HIV-1.

Based on available data on safety in pregnancy, zidovudine/lamivudine plus lopinavir/ritonavir is the preferred regimen [2]. Tenofovir plus emtricitabine with lopinavir/ritonavir can be considered as an alternative [5,6]. For additional information regarding prescribing ART for pregnant women, refer to Antiretroviral Therapy

For HIV-2-infected pregnant women who decline ART for their own health, but for whom prevention of MTCT is necessary, two NRTIs plus lopinavir/ritonavir is the recommended regimen [2]. Single-drug prophylaxis with zidovudine alone during pregnancy and intrapartum can be considered as an alternative for preventing HIV-2 MTCT [2]. All ART prescribing considerations, including postnatal ART management, for HIV-2-infected pregnant women should be in consultation with a provider who has experience in the management of ART in these patients.

Testing and Prophylaxis for HIV-2-Exposed Infants

RECOMMENDATIONS
  • All infants born to mothers infected with HIV-2 should receive the standard 6-week zidovudine prophylactic regimen [2,6]. (AIII)
  • Clinicians should advise HIV-2-infected women about the risk of postpartum MTCT via breast milk. Breastfeeding is contraindicated for both HIV-1- and HIV-2-infected mothers, even when receiving ART [7]. (AI)
  • The New York State Department of Health (NYSDOH) strongly recommends that all New York State birth facilities use the pediatric HIV testing services at the Wadsworth Center (see Diagnosis of Pediatric HIV Infection in HIV-Exposed Infants for the recommended diagnostic testing schedule).

In New York State, the Newborn Screening Program screens newborns for HIV-1 antibodies using a dried blood spot sample collected from a heel-stick. HIV-2 antibodies, if present in the blood spot, may be detected by the EIA test due to cross-reactivity. This may present as HIV-1 test results that are inconsistent, inconclusive, or negative despite clinical evidence that is consistent with immunodeficiency. All infants who are born to HIV-infected mothers or who test positive for HIV antibodies on the newborn screening test are considered to be exposed to HIV and must have additional testing to definitively diagnose or exclude HIV infection. A blood specimen should be obtained from all exposed infants and should be sent to the Pediatric HIV Testing Service at the NYSDOH Wadsworth Center for diagnostic testing. The Pediatric HIV Testing Service performs an immunoassay that differentiates between HIV-1 and HIV-2 antibodies on all infant samples. If the sample is reactive for HIV-2 antibodies, then a qualitative HIV-2 RNA test is performed to definitively diagnose or exclude HIV-2 infection. See Diagnosis of Pediatric HIV Infection in HIV-Exposed Infants for the recommended diagnostic testing schedule.

References:
  1. Burgard M, Jasseron C, Matheron S, et al. Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1. Clin Infect Dis 2010;51:833-843. [PubMed]
  2. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Sep. 14, 2011; pp 85-87. Available at http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf
  3. O’Donovan D, Ariyoshi K, Milligan P, et al. Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV. AIDS 2000;14:441-448. [PubMed]
  4. Morgan G, Wilkins HA, Pepin J, et al. AIDS following mother-to-child transmission of HIV-2. AIDS 1990;4:879-882. [PubMed]
  5. Gilleece Y, Chadwick DR, Breuer J, et al. British HIV Association guidelines for antiretroviral treatment of HIV-2-positive individuals 2010. HIV Med 2010;11:611-619. [PubMed]
  6. de Ruiter A, Mercey D, Anderson J, et al. British HIV Association and Children’s HIV Association guidelines for the management of HIV infection in pregnant women 2008. HIV Med 2008;9:452-502. [PubMed]
  7. Committee on Pediatric AIDS. Infant feeding and transmission of human immunodeficiency virus in the United States. Pediatrics 2013;131;391-396. [PubMed]

All Recommendations

Medical Care Criteria Committee, April 2012

ALL RECOMMENDATIONS: HIV-2
Screening and Diagnosis 
  • Specimens submitted for HIV testing should be screened by an enzyme immunoassay (EIA) that detects HIV-1, HIV-1 group O, and HIV-2. All laboratories performing HIV diagnostic testing should incorporate algorithms for differentiation of HIV-1 versus HIV-2 in repeatedly reactive samples. (AIII)
  • When HIV-1/HIV-2 combination screening yields a reactive result but is followed by indeterminate or nonreactive HIV-1 Western blot, clinicians should:
    • Obtain a plasma HIV RNA assay to exclude acute HIV-1 infection (AIII)
    • Obtain testing for HIV-2 antibodies with an FDA-approved HIV-1/HIV-2 type-differentiating immunoassay if acute HIV-1 infection has been excluded (AIII)
    • Consider specimens positive for HIV-2 if they are repeatedly reactive on an HIV-1/HIV-2 screening test and reactive for HIV-2 antibodies on the HIV-1/HIV-2 differentiation test (AIII)
  • Clinicians should use HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols when screening for HIV in patients who meet the criteria outlined in the text. (AIII)
Monitoring 
  • Clinicians should monitor HIV-2-infected patients by clinical evaluation and CD4 cell count. (BIII)
Treatment 
  • Clinicians should include two NRTIs and an appropriate boosted PI, such as lopinavir, saquinavir, or darunavir, when prescribing ART for HIV-2 mono-infected or HIV-1/HIV-2 co-infected individuals (see text). (AIII)
  • Clinicians should not prescribe NNRTIs or the PIs nelfinavir, atazanavir, or fosamprenavir as part of an ART regimen against HIV-2 mono-infection; these agents may be used as part of a regimen for HIV-1/HIV-2 co-infected patients if adequate treatment for HIV-2 is also included. (BIII)
  • Clinicians should consult with a provider with experience in the management of HIV-2 before initiating ART in HIV-2-infected patients. (AIII)
  • Clinicians should educate patients with confirmed HIV-2 infection about the lack of data regarding treatment of HIV-2 and should review individual benefits and risks of initiating treatment. Patients should make the final decision of whether and when to initiate ART.
Pregnancy 
  • Clinicians caring for pregnant patients with suspected or diagnosed HIV-2 should consult with a provider with experience in HIV-2 testing and management, including perinatal ART for HIV-2-infected pregnant women and postnatal ART for HIV-2-exposed infants. (AIII)
  • Clinicians should use HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols when screening for HIV in pregnant women who meet the criteria outlined in the text. (AIII)
  • Zidovudine plus lamivudine with lopinavir/ritonavir is the currently recommended regimen for HIV-2-infected pregnant women. (AIII)
  • For HIV-2-infected women who decline ART or who are unable to adhere to an ART regimen during pregnancy, single-drug prophylaxis with zidovudine during pregnancy and intrapartum should be used as an alternative for preventing HIV-2 mother-to-child transmission. (BIII)
  • All infants born to mothers infected with HIV-2 should receive the standard 6-week zidovudine prophylactic regimen. (AIII)
  • Clinicians should advise HIV-2-infected women about the risk of postpartum MTCT via breast milk. Breastfeeding is contraindicated for both HIV-1- and HIV-2-infected mothers, even when receiving ART. (AI)
  • The New York State Department of Health (NYSDOH) strongly recommends that all New York State birth facilities use the pediatric HIV testing services at the Wadsworth Center.

 

Selected Resources

For Care Providers

October 2016

EDUCATION

AIDSinfo: Training for Health Care Providers

AIDS Education Training Center (AETC):

HIV Testing in the Dental Chair: Technical Assistance Manual

Northeast/Caribbean AETC

Resource Library

Centers for Disease Control and Prevention (CDC):

HIV/AIDS Learning Center

HIV Testing

Public Health Image Library

E-patients.net: Salzburg Statement on Shared Decision Making

National Center for Transgender Equality: 2015 U.S. Transgender Survey

New York State Department of Health (NYSDOH):

CEI: HIV, HCV & STD Clinical Education Initiative

Emergency Contraception: What You Need to Know

NYS AIDS Institute Training Center

NYS Opioid Overdose Prevention Program

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Partner Services: What Health Care Providers Need to Know

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

What to do if You Have Been Raped or Sexually Assaulted

UCSF: HIV InSite

US Occupational Safety and Health Administration:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

US Department of Veterans Affairs:

Dermatological Manifestations of HIV Image Library

HIV/AIDS Image Library

Oral Manifestations of HIV Image Library

 

GUIDELINES

AHRQ: National Guideline Clearinghouse

AIDSinfo (DHHS guidelines): https://aidsinfo.nih.gov/

CDC HIV/AIDS Guidelines and Recommendations: http://www.cdc.gov/hiv/guidelines/

IAS-USA Practice Guidelines: https://www.iasusa.org/guidelines

 

LAW

CDC: NIOSH: Preventing Needlestick Injuries in Health Care Settings

New York City (NYC) Health: Reporting Diseases and Conditions

NYSDOH:

Communicable Disease Reporting Requirements

Court-Ordered HIV Testing of Defendants

Expedited Partner Therapy: A Guide for Partner Care

HIPAA Information Center

HIV Uninsured Care Programs: Summary

HIV/AIDS Laws & Regulations

HIV/AIDS Testing, Reporting and Confidentiality of HIV-Related Information

NYSDOH: Rules, Regulations & Laws

Office for the Prevention of Domestic Violence

Partner Services: What Health Care Providers Need to Know

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexually Transmitted Diseases

OSHA:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

US Courts: courtsystem.org

 

SERVICES

National Institutes of Health (NIH): Clinicaltrials.gov

New York City (NYC) Health: STD and HIV Services, including Clinic Locations and Hours

New York eHealth Collaborative: NYEC

New York State (NYS):

Council of Health-System Pharmacists (NYSCHP)

Department of Health

Office of Victim Services

AIDS Drug Assistance Program (ADAP) Formulary

AIDS Institute

Directory of ESAP Providers in New York State

Expanded Syringe Access Program (ESAP): Overview of Law and Regulations

HIV Testing

NYC: Life Net

NYC: Contact Notification Assistance Program (CNAP)

NYC: Expedited Partner Therapy

Medicaid Managed Care and Family Health Plus Pharmacy Benefit Information Center

NYC: Mayor’s Office for People with Disabilities

NYC: Mayor’s Office for People with Disabilities: American Sign Language Interpreters in New York

NYC Quits

NYS PrEP/PEP Provider Voluntary Director

NYS Expanded Syringe Access Program (ESAP)

NYS Safe Sharps Collection Program

NYSDOH HIV Uninsured Care Programs

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Rapid Testing for HIV

Sexual Assault Forensic Examiner (SAFE) Program

Smokers’ Quitline

STD Clinics in New York State

Wadsworth Center

What to do if You Have Been Raped or Sexually Assaulted

UCSF Clinician Consultation Center

HIV/AIDS Management

Submit for a case consultation

Phone consultation: 800-933-3413 (M-F, 9am-8pm EST)

US Occupational Safety and Health Administration:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

 

TOOLS

AIDSinfo: Drug Database

Antiretroviral Pregnancy Registry: For Health Care Providers

HIV Clinical Resource: 

HIV in Older Adults: Quick Reference Guide

Insomnia Screening & Treatment Quick Reference Guide

Mental Health Screening: Quick Reference Guide

Provider Guide to HIV Testing Quick Reference Card

Substance Use Screening: Quick ReferenceGuide

NYSDOH: CEI: HIV, HCV & STD Clinical Education Initiative

University of Liverpool: HIV Drug Interactions

UCSF HIV InSite: Database of Antiretroviral Drug Interactions

For Consumers

October 2016

EDUCATION

AIDSinfo Fact Sheets (English and Spanish): https://aidsinfo.nih.gov/education-materials/fact-sheets/

AIDSinfo Infographics:

Antiretroviral Therapy . . . What does it do?

HIV and AIDS: What’s the Difference?

HIV and Birth Control

HIV Discordant Couples

HIV Drug Resistance

Living with HIV: Steps to Better Health

Protecting Baby from HIV

What Do My Lab Results Mean?

Three Things to Know about HIV Treatment

Centers for Disease Control and Prevention (CDC): HIV Basics

E-patients.net: Salzburg Statement on Shared Decision Making

Fenway Health: Transgender Health

HIV-Age: Aging with HIV

NAM Aidsmap: HIV Basics

New York State Department of Health (NYSDOH):

Directory of ESAP Providers in New York State

Emergency Contraception: What You Need to Know

NYS Opioid Overdose Prevention Program

NYS Safe Sharps Collection Program

NYSDOH HIV Uninsured Care Programs

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

What to do if You Have Been Raped or Sexually Assaulted

Target Center: Tools for the Ryan White Community

The Body: The Complete HIV/AIDS Resource

UCSF: 

HIV InSite

Center of Excellence for Transgender Health

US Occupational Safety and Health Administration (OSHA):

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

US Department of Veterans Affairs:

Dermatological Manifestations of HIV Image Library

HIV/AIDS Image Library

Oral Manifestations of HIV Image Library

 

GUIDELINES

AHRQ: National Guideline Clearinghouse

AIDSinfo (DHHS guidelines): https://aidsinfo.nih.gov/

CDC HIV/AIDS Guidelines and Recommendations: http://www.cdc.gov/hiv/guidelines/

IAS-USA Practice Guidelines: https://www.iasusa.org/guidelines

 

LAW

New York State (NYS): Office for the Prevention of Domestic Violence

NYSDOH:

HIPAA Information Center

HIV Testing

HIV Uninsured Care Programs: Summary

HIV/AIDS Laws & Regulations

HIV/AIDS Testing, Reporting and Confidentiality of HIV-Related Information

PrEP and PEP Information & Resources

Rape Crisis and Sexual Violence Prevention Program

Sexually Transmitted Diseases

OSHA:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

US Courts: courtsystem.org

 

SERVICES

National Institutes of Health (NIH): ClinicalTrials.gov

NYC Health

Life Net

NYC Quits

STD and HIV Services, including Clinic Locations and Hours

New York State:

Directory of ESAP Providers in New York State

Emergency Contraception: What You Need to Know

Expanded Syringe Access Program (ESAP): Overview of Law and Regulations

HIPAA Information Center

HIV Testing

HIV Uninsured Care Programs: Summary

New York State PrEP/PEP Provider Voluntary Director

NYS Expanded Syringe Access Program (ESAP)

NYS Opioid Overdose Prevention Program

NYS Safe Sharps Collection Program

NYSDOH HIV Uninsured Care Programs

Office for the Prevention of Domestic Violence

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Office of Victim Services

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

STD Clinics in New York State

What to do if You Have Been Raped or Sexually Assaulted

OSHA:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

All FDA-Approved HIV Medications

January 10, 2017

Listed below are all FDA-approved HIV medications as of April 17, 2016, with links to the AIDSinfo drug database. For professionals, the links open the FDA label pages, and for consumers, the links open the AIDSinfo patient information pages. The list is organized by drug class, with individual drugs listed in alphabetical order. Combination drugs are also listed in alphabetical order.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs): characteristics
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): characteristics
Protease Inhibitors (PIs): characteristics
Fusion Inhibitor: characteristics
Entry Inhibitor: characteristics
Integrase Inhibitors (INSTIs): characteristics
Pharmacokinetic Enhancer:
Combination HIV Medications:

HIV Care Provider Definitions

New York State Department of Health AIDS Institute, April 2017

Experienced HIV care provider: Practitioners who have been accorded HIV-Experienced Provider status by the American Academy of HIV Medicine (AAHIVM) or have met the HIV Medicine Association’s (HIVMA) definition of and experienced provider are eligible for designation as an HIV Experienced Provider in New York State.

Nurse practitioners and licensed midwives who provide clinical care to HIV-Infected individuals in collaboration with a physician may be considered HIV Experienced Providers provided that all other practice agreements are met (8 NYCRR 79-5:1; 10 NYCRR 85.36; 8 NYCRR 139-6900)

Physician assistants who provide clinical care to HIV-infected individuals under the supervision of an HIV Specialist physician may also be considered HIV Experienced Providers (10 NYCRR 94.2)

Expert HIV care provider: A provider with extensive experience in the management of complex patients with HIV.

June 2016 Policy Statement: Defining Program Eligibility by HIV Status

NYSDOH-Policy-Statement_Defining-Program-Eligibility-by-HIV-Status_6-23-2016_with-link-to-pr

 

Q/A: HIV Window Period, Testing, PEP, and Acute Infection

Updated January 2016

Window Period

windowperiod-q-a_pdf
Download PDF

What is the “window period”? The “window period” occurs between the time of HIV infection and the time when diagnostic tests can detect HIV. The length of the window period varies depending on the type of diagnostic test used and the method the test employs to detect the virus.

Can an infected person transmit HIV to others during the window period? Yes. During the window period, and despite a negative test result, an HIV-infected person may transmit the virus to others.

How long can the window period last? The window period varies slightly from person to person, but virtually everyone infected with HIV develops antibodies within 3 months of infection.

When is follow-up HIV testing warranted? If a person tests negative for antibodies 3 months after a potential exposure to HIV, he or she does not require further testing. However, follow-up testing is warranted for individuals with repeated potential exposures during that 3-month period or when the antibody test results are incompatible with the person’s clinical history.

HIV Testing

What are the recommendations for routine HIV testing for adults? The New York State Department of Health (NYSDOH), the US Centers for Disease Control and Prevention (CDC), and the US Preventive Services Task Force (USPSTF) recommend offering HIV testing to all adults as part of routine healthcare. New York State law requires that all persons between the ages of 13 and 64 be offered an HIV test at least once. The law also requires healthcare providers to offer an HIV test to any person, regardless of age, if there is evidence of risk activity.

Who should be offered ongoing HIV testing? Testing should be offered at least annually to anyone whose behavior increases his or her risk for exposure to HIV. Since many people choose not to disclose their risk behaviors, providers should consider adopting a low threshold for recommending the test.

How often should individuals who engage in high-risk behavior be tested? Clinicians should recommend testing every 3 months for individuals who engage in unprotected anal sex, sex with multiple or anonymous partners, needle-sharing, or sex with partners who share needles. In these high-risk cases, testing is used to ensure early access to care and to prevent transmission to others if the patient becomes infected.

Should pre-exposure prophylaxis (PrEP) be offered to individuals with high-risk behavior? Yes. PrEP to prevent HIV infection should be considered for persons with ongoing high-risk behaviors. PrEP should be prescribed as part of a comprehensive prevention strategy that includes risk-reduction counseling about safer sex practices, condom use, and safer injection practices, as well as referral to syringe exchange programs and drug treatment services when appropriate. The NYSDOH AIDS Institute guidance for PrEP is available online.

KEY POINT
NYSDOH, CDC, and USPSTF recommend HIV testing for all adults as a routine part of healthcare.

HIV Diagnostic Testing Algorithm

What is the HIV diagnostic testing algorithm? This is a laboratory-based diagnostic algorithm that recommends a combination of laboratory tests performed in a defined sequence. Extensive evidence supports this algorithm for maximal sensitivity, specificity, and accuracy for HIV detection.

What is the initial test of the HIV diagnostic testing algorithm? The algorithm begins with an immunoassay (sometimes called a “4th generation test”) that detects both HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen. The HIV-1 p24 antigen appears before antibodies develop so that acute HIV infection can sometimes be detected.

What steps are taken when the initial test is reactive? Specimens reactive on the initial assay are tested with a supplemental assay that differentiates HIV-1 and HIV-2 antibodies. Specimens that are reactive on the initial assay but nonreactive or indeterminate on the antibody differentiation assay are then tested for HIV-1 RNA to differentiate acute HIV infection from a false-positive screening result. The final interpretation is based on a combination of test results. The NYSDOH Testing Toolkit provides more information about HIV diagnostic tests and the algorithm. The NYSDOH AIDS Institute’s guidelines on HIV testing and monitoring patients on ART should be consulted as well.

KEY POINT
It is important to know which HIV tests are being used by your agency or laboratory so you can provide patients with accurate information regarding their HIV test results.

Exposure to HIV and Post-Exposure Prophylaxis (PEP) 

What are the recommendations for persons who report an exposure? HIV exposure is a medical emergency. If the patient reports a significant exposure, the first dose of PEP should be given. Other testing and evaluation can be continued following the first dose. When PEP is initiated immediately after an exposure (ideally, within 2 hours), it can prevent HIV infection. Please consult the NYSDOH AIDS Institute’s clinical guidelines on PEP for prevention of HIV infection.

PEP is most likely to prevent infection when initiated within 36 hours of exposure. The decision to start PEP later, beyond 36 hours post-exposure, should be made jointly by the clinician and the exposed individual, with the understanding that PEP is less likely to prevent HIV infection the longer it is delayed.

Can HIV infection be detected immediately after exposure? HIV infection is not immediately detectable.

How often should an exposed individual be tested? NYSDOH protocols recommend testing at baseline and at 4 and 12 weeks post-exposure.

Are the guidelines for PEP different for different types of exposure? The NYSDOH AIDS Institute provides specific guidelines for PEP following occupational exposure, non-occupational exposure, and sexual assault.

Acute HIV Infection

What is acute HIV infection? Acute HIV infection is the very early, initial stage of HIV infection when the virus is multiplying rapidly and the body has not yet developed antibodies to fight it.

What are the symptoms of acute HIV infection? Symptoms of acute HIV infection are similar to flu symptoms and may include fever, fatigue or malaise, joint pain, headache, loss of appetite, rash, night sweats, myalgia, nausea or diarrhea, and pharyngitis.

If acute HIV infection is suspected, what steps should be taken for testing? If a patient presents with signs/symptoms of acute HIV, then HIV RNA testing should be requested in conjunction with an initial 4th generation (recommended) or 3rd generation (alternative) screening test. In the absence of serologic evidence of HIV infection:

  • If HIV RNA is not detected, no further testing is needed.
  • Detection of HIV RNA with ≥5,000 copies/mL indicates a preliminary diagnosis of HIV infection.
  • Detection of HIV RNA with <5,000 copies/mL requires repeat HIV RNA testing.
  • If a diagnosis of HIV infection is made on the basis of HIV RNA testing alone, a new specimen should be collected 3 weeks later, and HIV diagnostic testing should be repeated.
KEY POINT
When acute infection is suspected, an HIV RNA assay should always be requested in conjunction with an HIV screening test.

Why is it so important to diagnose HIV infection during the acute phase? In most infected persons, HIV viral load increases quickly after exposure, peaks at about 3 weeks post exposure, and then declines over the next several months. An HIV-infected person is most infectious during this acute phase because of the high viral load. The NYSDOH AIDS Institute clinical guideline on Diagnosis and Management of Acute HIV Infection recommends ART for all patients diagnosed with HIV infection.

Is specialty consultation required for pregnant women with acute HIV infection? Yes. If acute HIV infection is suspected in a pregnant woman, request HIV RNA testing in addition to a 4th generation (recommended) or 3rd generation (alternative) screening test. If reactive, consultation with a provider experienced in diagnosing and evaluating acute HIV infection is important. Earlier diagnosis and treatment can reduce the risk of mother-to-child transmission. For more information, see Acute HIV Infection in Pregnancy.

How can I locate an experienced HIV care provider? The CEI line, which is available through the NYSDOH Clinical Education Initiative, provides access to providers with experience in acute HIV infection: 866-637-2342.

HCV CARE

The Hepatitis C Virus Infection Guideline Committee produced the HCV guidelines

  • NYSDOH Dear Colleague Letter: Increases in HCV infection among women of childbearing age → Learn More   
  • Note: An updated guideline on treatment and management of HCV is in production, with publication expected in Spring 2017. Subscribe to our mailing list to receive e-mail notification of publication.
  • CEI provides progressive HIV, HCV, and STD CME for health care providers → Learn More 

Definition of an Experienced | HCV Care Provider

 

 

NYS Provider Directory

NYSDOH Dear Colleague Letter of January 2016 (click to download PDF)

Dear HCV Provider,

As you may be aware, in early 2015, the NYSDOH AIDS Institute launched a web-based public directory of experienced HIV care practitioners in New York State. We are excited to announce this directory has now been expanded to include experienced HCV care practitioners. We encourage all HCV practitioners in New York State to register for the purpose of providing the public with information about where patients living with HCV can access experienced providers within the State.

Participation in this directory is voluntary. It is compiled through provider self-identification, and includes physicians, nurse practitioners, physician assistants, and doctors of osteopathic medicine with experience in HCV care and treatment and who meet the NYSDOH definition of an experienced HCV provider. Please note that this list in no way constitutes credentialing or certification in a specialty. Inclusion in this list does not confer any endorsement by the New York State Department of Health. We confirm that practitioners are licensed to practice in New York State.

If you are interested in being listed in this directory, please follow the steps outlined below to register through our on-line registration system. We will email you annual reminders to confirm/update your contact information. You are able to withdraw your name from this directory at any time. If you already participate in the directory as an HIV provider and would also like to register as an HCV provider, simply log into HCS and update your record with your HCV-related information.

To register: First you must log on to the NYSDOH Health Commerce System (HCS). If you do not already have an account or need help accessing your HCS account, please send an email to hcsoutreach@health.state.ny.us.

Step 1: Log on to HCS at https://commerce.health.state.ny.us.

Step 2: Click ‘My Content’ -> ‘All Applications’.

Step 3: Click letter ‘H’ and select ‘HIV/HCV Provider Directory’.

Step 4: Follow the instructions as provided on the screen. Step 5: Email hivproviderdirectory@health.ny.gov with any questions or concerns.

The public listing of the directory will include providers’ names, contact information, and credentials as an HIV and/or HCV specialist (if applicable). This directory will be made available to the public online and will be updated at the beginning of each month.

Finally, please forward this invitation to any HCV or HIV care provider who may be interested in registering themselves in the directory. We thank you for your time and wish you all the best.

Sincerely,

AIDS Institute, Viral Hepatitis Section

Qualifications

The components below were developed by the New York State Department of Health AIDS Institute’s Hepatitis C Clinical Guidelines Committee to define those healthcare providers who are qualified to prescribe hepatitis C antiviral therapy.

Clinical experience and appropriate continuing education are both important to ensure that HCV medications are prescribed safely and correctly and that all patients receive the highest quality of care.

New York State Qualifications for Prescribing HCV Antiviral Therapy

Providers must meet all three criteria.

Clinical experience:

  • Management AND treatment of at least 10 patients with HCV infection within the past 12 months OR 
  • Management and treatment of 10 patients with HCV infection in partnership (defined as consultation, preceptorship, or via telemedicine) with an experienced HCV provider who meets the above criteria.

Continuing Medical Education: At least 10 HCV-related CME credits in the last 12 months.

Licensure: A current, valid MD, DO, PA, or NP New York State license.

Questions and Answers

Why has the New York State Department of Health AIDS Institute (NYSDOH AI) developed criteria for defining the experienced HCV provider?  The NYSDOH AIDS Institute (AI) is responsible for ensuring a statewide standard of care for treatment and management of patients with HCV. The AI has developed criteria for defining experienced HCV providers to ensure that patients with HCV are treated by clinicians with the appropriate level of expertise to deliver necessary care that meets current quality standards.

Who developed the criteria for this definition? The criteria for defining the experienced HCV provider were developed by the NYSDOH AI’s Hepatitis C Clinical Guidelines Committee.

If a medical practitioner is already licensed or board certified in NYS, why are these criteria necessary? No formal certification program exists for HCV expertise or experience. Promulgation of these criteria for NYS will establish consistent criteria for determining capability and will ensure that quality treatment is delivered by experienced providers.

Does a provider need to meet both experience and CME criteria to qualify as an experienced HCV experienced provider? If a provider fails to meet these criteria, should he or she not care for or provide treatment to persons diagnosed with HCV? To qualify as an experienced HCV provider, both criteria must be met. If a provider lacks necessary experience in managing or treating HCV patients, he or she may work in partnership with an HCV-experienced provider to deliver care and treatment through consultation or mentorship. If such a co-management relationship can be arranged, patients do not need to be referred to a new HCV provider.

Do patients count toward meeting the criteria if they are being managed or treated through a mentoring, consultative, or telemedicine relationship? Yes.

How long must a provider work in partnership with an experienced HCV provider before he or she can be considered an experienced provider? Based on the criteria, it is recommended that, at a minimum, providers work in partnership until they have managed AND treated 10 patients over a 12-month period. However, the partnership should continue for as long as the provider feels it necessary. An ongoing mentoring relationship or on-demand consultations may be beneficial, even though the minimum criteria have been met. To identify resources for mentoring, providers should contact the NYS HIV, HCV and STD Clinical Education Initiative at www.ceitraining.org. In addition, the CEI Line (866-637-2342) provides clinicians free consultation with specialists to discuss HCV management.

Is there any evidence that working in partnership with an experienced HCV provider results in similar patient outcomes? Since 2010, the AIDS Institute has been funding primary care sites to integrate HCV care and treatment. In each of these settings, the model includes a primary care provider (PCP) and a multidisciplinary team to manage and treat persons infected with HCV. Each PCP works in partnership with an experienced HCV provider to gain the knowledge, skills, and experience to safely and effectively manage and treat HCV. Data from these programs demonstrate that PCPs are able to gain the knowledge and skills needed for successful HCV care [1]. In addition, Project ECHO (Extension for Community Healthcare Outcomes) is an effective model developed by the University of New Mexico Health Sciences Center that uses state-of-the-art tele-health technology, best practice protocols, and case-based learning to train and support primary care providers. This model has shown improved outcomes following coaching and mentoring by an experienced provider [2].

Do the criteria have to be fulfilled only once or every year? The criteria must be met for each 12-month period. For example, if a provider co-manages and treats the minimum number of HCV patients in 2014, that provider would be eligible to manage and treat HCV patients by him- or herself in 2015. If the provider does not meet the minimum requirements, he or she would have to continue to co-manage in 2015. The changing nature of HCV therapeutics requires that clinicians keep up to date with their use.

Do providers meeting these criteria receive enhanced Medicaid reimbursement when providing HCV care and treatment services? No. There is no enhanced reimbursement through Medicaid or other state programs for providers meeting the criteria for experience in HCV management and treatment.

How do these criteria for experienced HCV providers relate to the clinical criteria established by NYS Medicaid and the Managed Care Organizations for prior authorizations of HCV medications? The criteria for experienced HCV providers have been reviewed by both NYS Medicaid and Managed Care Organizations. On October 16, 2014, the NYS Medicaid fee-for-service (FFS) pharmacy program implemented these criteria as well as additional clinical criteria for prior authorization to prescribe HCV medication therapy. Information about the clinical criteria for HCV drug therapy can be found in the NYSDOH Medicaid October 2014 Update.

Are providers required to register as experienced HCV providers before they can prescribe HCV medications? If so, how can they register? No. As part of the prior authorization (PA) process, prescriber experience and training must be verified. To streamline the PA process, the NYSDOH developed an HCV Approved Practitioners List, which can be used by the Medicaid FFS PA call center as well as all of the Medicaid Managed Care plans. If a provider is on the list, the criteria have been satisfied. If a provider is not on the list, additional information must be provided to ascertain his or her level of experience. Providers can register to be put on the list by filling out the Medicaid Hepatitis C Practitioner Information Request Form on the NYSDOH website.

How can patients find an experienced HCV provider? The NYSDOH AI will publish a voluntary directory of experienced HCV providers in 2015 so that providers and patients can easily locate an experienced HCV provider.

Will the NYSDOH AI issue guidelines on the management and treatment of patients with HCV? Yes. The AIDS Institute is currently updating its guidelines on the management and treatment of HCV patients. The guidelines are expected to be released in 2016. They will be available on the NYSDOH Hepatitis website at and on this website.

If providers have additional questions regarding the criteria, whom should they contact? Additional questions regarding the criteria can be sent to: hepatabc@health.ny.gov.

References

  1. Flanigan CA and Hart-Malloy R. Evaluating the Quality of HCV Care and Treatment in Primary Care Settings. American Association for the Study of Liver Disease Conference, Washington, DC, abstract 2067, November 2013.
  2. Arora S, Thornton K, Murata G, et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med2011;364:2199-2207. [PubMed]

 

Should You Be Tested?

Why You Should Be Tested for Hep C

May 2014

Hepatitis C Consumer Testing Card (Click to download)

This double sided card is aimed at increasing hepatitis C screening among persons at-risk for hepatitis C, including those born between 1945 and 1965. The card outlines who should be screened for hepatitis C and includes information on the hepatitis C screening methods and test result interpretations.

Why You Should Be Tested for Hep C

There are things you can do to fight hepatitis C. Early detection can help. Knowing your hep C status will help prevent transmission to others. Hep C is a curable condition for most people. Better treatments are available with fewer side effects.

Even if you do not start treatment, there are a few things you can still do to keep your liver healthy, such as avoiding alcohol and getting vaccinated for hepatitis A and B. 

GET TESTED
For a list of free hepatitis C testing sites in New York State go to: www.health.ny.gov/hepatitis

What is Hepatitis C?

March 2014

Download the Hepatitis C Consumer Testing Card 

Hepatitis C (Hep C) is a liver disease caused by the hepatitis C virus. Hepatitis C can lead to serious liver damage. Hepatitis C progresses slowly and often has no symptoms. Many people have hepatitis C and don’t know it. The only way to know if you have hepatitis C is to get tested.

Get Tested for Hepatitis C If You . . .

  • Injected drugs, even just once many years ago
  • Were born from 1945-1965 (Baby Boomers)*
  • Received donated blood or organs before 1992
  • Received clotting factor before 1987
  • Got a tattoo or body piercing from an unlicensed artist, such as on the street or while in jail
  • Are HIV positive
  • Were exposed to blood on the job through a needlestick or injury with a sharp object
  • Were ever on long-term dialysis
  • Snorted drugs

*In New York State, health care providers are required by law to offer anyone born between 1945 and 1965 a test for hepatitis C.

GET TESTED
For a list of free hepatitis C testing sites in New York State go to: www.health.ny.gov/hepatitis

 

Hepatitis C Antibody Test and Results

March 2014

Download the Hepatitis C Consumer Testing Card 

A hepatitis C antibody test is a blood test that looks for antibodies to the hepatitis C virus. The test can be done by collecting a blood sample and sending it to a lab, or by a fingerstick using a hepatitis C rapid antibody test. The hepatitis C antibody test will tell you if you have ever been infected with hepatitis C. You may need a second test to know if you are currently infected.

If the test result is NON-REACTIVE/NEGATIVE:

  • A non-reactive or negative antibody test means that you are not currently infected with the hepatitis C virus.
  • However, if you have engaged in risky behavior in the last 6 months, you will need to be tested again.
  • Your non-reactive test result does not protect you from getting hepatitis C in the future.

If the test result is REACTIVE/POSITIVE:

  • A reactive or positive antibody test means that you have antibodies to hepatitis C in your blood.
  • You were exposed to hepatitis C at one time. You are probably infected with hepatitis C.
  • You will need a second test to know for sure.

Take the second test–KNOW FOR SURE:

  • This second test is called an RNA test. Another name used for this test is a PCR test. The RNA test checks for hepatitis C virus in your blood.
  • If you don’t have the virus in your blood, this test will come back undetectable. If the test comes back detectable, then you have hepatitis C.
GET TESTED
For a list of free hepatitis C testing sites in New York State go to: www.health.ny.gov/hepatitis

For Care Providers

October 2016

EDUCATION

E-patients.net: Salzburg Statement on Shared Decision Making

New York State Department of Health (NYSDOH):

CEI: HIV, HCV & STD Clinical Education Initiative

Communicable Disease Reporting Requirements

Directory of ESAP Providers in New York State

Hepatitis C

NYS AIDS Institute Training Center

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

US Occupational Safety and Health Administration:

Bloodborne Pathogens & Needlestick Prevention

Enforcement Procedures for Occupational Exposure to Bloodborne Pathogens

University of Washington: Hepatitis C Online

NYSDOH/NYC DOHMH Patient Education Material: These message pads are designed for persons performing HCV screening/counseling to ensure that counseling messages appropriate for specific screening test results are delivered.

Non-Reactive Result/Antibody Negative 

Reactive Result/Antibody Positive 

 

GUIDELINES

AASLD/IDSA: HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C

CDC:

Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease

Recommended HCV Testing Sequence

US Department of Veterans Affairs: Viral Hepatitis Guidelines and Best Practices

 

LAW

NYSDOH:

Communicable Disease Reporting Requirements

Hepatitis C

HIPAA Information Center

 

SERVICES

National Institutes of Health (NIH): ClinicalTrials.gov

New York eHealth Collaborative: NYEC

New York State (NYS):

Office for the Prevention of Domestic Violence

Office of Victim Services

NYSDOH:

Directory of ESAP Providers in New York State

Expanded Syringe Access Program (ESAP): Overview of Law and Regulations

HCV Rapid Testing Program

Hepatitis C

NYS Safe Sharps Collection Program

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Wadsworth Center

 

TOOLS

Alcohol and Drug Use Screening Tools:

AUDIT-C 3-item alcohol screen

CAGE Questionnaire

Addiction Severity Index Lite-CF

SAMSHA: Screening, Brief Intervention, and Referral to Treatment (SBIRT)

WHO: Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)

Classifying the Severity of Cirrhosis:

Model for End-Stage Liver Disease (MELD) Calculator

Child-Turcotte-Pugh (CTP) Calculator

NYSDOH: CEI: HIV, HCV & STD Clinical Education Initiative

Treatment Readiness Evaluation: Psychosocial Readiness Evaluation and Preparation for HCV Treatment (PREP-C)

ADOLESCENT HIV CARE

The Subcommittee on the Care of Adolescents with HIV Infection produced the adolescent HIV guidelines

  • FDA Updates Stribild Label to Include Peds (1/31/17) → Learn More
  • CEI provides progressive HIV, HCV, and STD CME for health care providers → Learn More 
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Disclosure to Parents | and Consent to Treat Guideline

Introduction

Subcommittee on the Care of Adolescents with HIV Infection, November 2012

The primary goal for clinicians who treat HIV-infected minors is to provide appropriate care that minimizes HIV disease progression. Although most medical treatment for HIV-infected minors requires parental or guardian disclosure, the rare situation may arise when someone under 18 years of age who is ineligible to consent to care has not disclosed his/her HIV status to a parent or legal guardian. This chapter aims to provide guidance on how to engage youth in the process of disclosing to parents or legal guardians and how to medically manage these patients while resolving issues of consent.

Adolescent Consent According to New York State Law

November 2012

RECOMMENDATIONS
  • Whenever possible, clinicians should obtain parental or legal guardian consent for HIV-related treatment for adolescents under 18 years of age who may be unable to consent to care according to New York State law.
  • Clinicians should be versed in New York State laws regarding consent and confidentiality for adolescents under 18 years of age and should educate their HIV-infected adolescent patients about these laws. (AIII)
  • Clinicians should refer to their institutional policy or consult with the institution’s legal department regarding adolescents under 18 years of age who refuse to disclose their HIV status to their parents or legal guardians and may be unable to consent to care according to New York State law.

Minors Who Are Eligible to Consent to HIV Treatment

RECOMMENDATION
  • Clinicians should encourage adolescents who consent to their own care to identify an adult who can provide support.

According to New York State Public Health Law, any person who is 18 years of age or older or who is the parent of a child or who is married may give effective informed consent to HIV-related treatment. Any minor who is pregnant may give consent to prenatal care (including HIV-related treatment or termination of pregnancy) [1].

Minors Who Are Ineligible to Consent to HIV Treatment

RECOMMENDATION
  • Clinicians should clearly document discussions regarding consent and disclosure of HIV status to parents and legal guardians in the HIV-infected adolescent’s medical record. (AIII)

For minors who are ineligible to consent to HIV treatment and who are not ready or who choose not to disclose their status to their parents or legal guardians, a multidisciplinary approach is often required to successfully engage these youth in the process of disclosing to parents or guardians. Clinicians who provide care for HIV-infected adolescents should be versed in New York State laws regarding adolescent consent and confidentiality and should refer to their institution’s policy regarding adolescents under 18 years of age who refuse to disclose their HIV status to their parents or legal guardians. Consultation with the institution’s legal department may be required for patients with special circumstances or when a policy for adolescent consent has not been established.

Reference:
  1. New York Public Health Law Section 2504.

Medical Management and Engagement in the Process of Disclosure

November 2012

Adolescents who have not yet discussed their HIV status with their parents or legal guardians and who may be unable to consent to care according to New York State law should receive education about the importance of remaining in care and should receive medical services to which they may consent, including:

  • Standard disease monitoring (e.g., physical and laboratory assessments such as CD4 counts and viral load tests)
  • STI screening and treatment
  • Family-planning services
  • Risk-reduction, mental health, and substance use counseling

Under most circumstances, antiretroviral therapy (ART) and other HIV-related medications may not be prescribed without parental or guardian consent. When the clinician believes that it is medically necessary to initiate ART or other HIV-related medications for a minor who will not disclose to his/her parent or legal guardian and the minor understands his/her condition, including the risks, benefits, and treatment options, every effort should be made to engage the patient in a dialogue with the goal of disclosure to parents or legal guardians. Although parental or legal guardian consent should be obtained before initiating ART, the clinician may not disclose confidential HIV-related information if, in the judgment of the clinician, the disclosure would not be in the best interest of the minor [1]. Such a disclosure may also jeopardize the patient-provider alliance, as well as the patient’s future acceptance of care.

A dialogue with the patient involving the long-term goal of disclosure to parents or legal guardians is necessary for establishing conditions for a minor’s HIV treatment. Determination of whether a minor’s health or well-being may be at risk if he/she discloses to his/her parent or legal guardian is part of establishing a framework for patient care. For example, a young man who has sex with men (YMSM) may risk being forced out of his home if he discloses his HIV status, and thereby his sexual identity, to his parents or legal guardians; or a female adolescent who has acquired HIV through sexual transmission may fear physical abuse if her family learns of her sexual activity.

KEY POINTS
  • Adolescent patients may be at risk for abuse if they disclose their HIV status. Appropriate referrals and assistance should be offered to patients reporting such risks.
  • Discussions about disclosure and possible risks to the adolescent should be documented in the medical record.
  • Coordination with insurance companies is necessary to ensure that confidentiality is managed according to patients’ wishes.

Many healthcare facilities have established policies and procedures to determine how to obtain consent for minors to receive HIV care. In the absence of such policies and procedures in their facilities, clinicians should seek consultation with their facility’s legal or risk management departments.

Clinicians should educate HIV-infected adolescents about the importance of working with their insurance plan’s member services regarding the following rights:

  • To “opt out” of explanations of benefits (EOBs) that are mailed to their parents or legal guardians regarding HIV care
  • To request that insurance cards be mailed to an alternate address
  • To ensure that information is not inadvertently disclosed through electronic portals that parents or legal guardians may be able to access

The NYSDOH AIDS Institute’s Dear Colleague Letter (May 21, 2012) provides information about minors’ confidentiality rights with insurance companies.

See NYSDOH HIV/AIDS Laws & Regulations for information on laws pertaining to HIV/AIDS testing, reporting, and confidentiality.

Reference:
  1. New York Public Health Law Section 2782(4)(e).

All Recommendations

Subcommittee on the Care of Adolescents with HIV Infection, November 2012

ALL RECOMMENDATIONS: DISCLOSURE TO PARENTS AND CONSENT
  • Whenever possible, clinicians should obtain parental or legal guardian consent for HIV-related treatment for adolescents under 18 years of age who may be unable to consent to care according to New York State law.
  • Clinicians should be versed in New York State laws regarding consent and confidentiality for adolescents under 18 years of age and should educate their HIV-infected adolescent patients about these laws. (AIII)
  • Clinicians should refer to their institutional policy or consult with the institution’s legal department regarding adolescents under 18 years of age who refuse to disclose their HIV status to their parents or legal guardians and may be unable to consent to care according to New York State law.
  • Clinicians should encourage adolescents who consent to their own care to identify an adult who can provide support.
  • Clinicians should clearly document discussions regarding consent and disclosure of HIV status to parents and legal guardians in the HIV-infected adolescent’s medical record. (AIII)

Disclosure to Perinatally | Infected Adolescents Guideline

Introduction

Subcommittee on the Care of Adolescents with HIV Infection, November 2009

RECOMMENDATION
  • Clinicians and other members of the multidisciplinary team should collaborate with caregivers of HIV-infected children to disclose the diagnosis of HIV to the child in a developmentally appropriate manner. (AIII)

One of the most difficult issues that families with HIV-infected children face is when and how to talk about HIV to their children. HIV disclosure to infected children and adolescents should take place in a supportive environment with collaboration and cooperation among caregivers and providers. Disclosure is contingent on the caregiver’s acknowledgment of the illness, the readiness to disclose, and the child’s cognitive skills and emotional maturity.

Some studies have shown that children who are able to discuss their illness with adults have fewer behavior problems and have improved social functioning, school performance, and adherence to medications [1,2]; however, other studies have shown an increase in behavior problems and stress levels after disclosure [3,4]. Poor adjustment to a chronic illness can be a barrier to adherence and may cause conflict between the child, the caregiver, and the healthcare team. Collaboration among providers and caregivers helps to ensure that a plan is in place to provide support to the child who learns about his or her HIV status. Developmentally appropriate and truthful explanations of the illness, validation of the child’s concerns about the disease, clarifications of misconceptions, and ongoing support are the cornerstones for promoting a positive adjustment to living with HIV infection.

This guideline addresses the following:

  • Collaboration with caregivers to create a disclosure plan
  • Age-specific considerations for disclosure
  • Ways in which providers can prepare families for the disclosure discussion
  • Considerations for disclosing to adolescents
  • Follow-up visits to provide support and to monitor the child’s/adolescent’s emotional adjustment and understanding of the illness
KEY POINT
Identification of one member of the multidisciplinary team who is trained as the “disclosure specialist” may facilitate the disclosure process. Many multidisciplinary teams include a psychologist or other mental health professional who may be uniquely suited to this role.
References:
  1. Nehring W, Lashley F, Malm K. Disclosing the diagnosis of pediatric HIV infection: Mothers’ views. J Soc Pediatr Nurs 2000;5:5-14. [PubMed]
  2. Blasini I, Chantry C, Cruz C, et al. Disclosure model for pediatric patients living with HIV in Puerto Rico: Design, implementation, and evaluation. J Dev Behav Pediatr 2004;25:181-189. [PubMed]
  3. Funck-Brentano I, Costagliola D, Seibel N, et al. Patterns of disclosure and perceptions of the human immunodeficiency virus in infected elementary school-age children. Arch Pediatr Adolesc Med 1997;151:978-985. [PubMed]
  4. Shaffer A, Jones DJ, Kotchick BA. Telling the children: Disclosure of maternal HIV infection and its effects on child psychosocial adjustment. J Child Family Studies 2001;10:301-313.

When to Begin the Disclosure Process

November 2009

RECOMMENDATION
  • Ongoing dialogue between the clinical team and caregivers regarding disclosure of HIV diagnosis and health concepts should occur early in the patient’s childhood. (AIII)

The American Academy of Pediatrics (AAP) encourages the disclosure of HIV infection status to school-aged children [1]. Most children without cognitive deficits have the capacity to understand the diagnosis and concepts about immune systems and health. Disclosure can help children understand the illness and may further a child’s willingness to adhere to his/her treatment regimen. A disclosure plan also prevents an accidental disclosure from occurring, such as when the child overhears the caregiver discussing the illness. Children who accidentally learn of their diagnosis may have a more difficult time adjusting to it [2].

Once the diagnosis has been explained to a child, it needs to be reinforced or regularly discussed as the child develops because many children will not have understood the full implications of the disease or diagnosis at the time of disclosure. For example, preadolescent children can cognitively understand the concepts about the virus but may be less likely to think of the future implications, such as transmission risks and safe sexual practices. As the child ages and matures, he/she will slowly understand and integrate the implications of the diagnosis into his/her life. Children’s perception of self, health, illness, and death evolve as they mature through different developmental stages. Knowledge of these different developmental stages can help guide clinicians and caregivers when discussing HIV with infected children and non-infected siblings.

KEY POINT
Disclosure of HIV status is not a one-time event, but rather a process, involving ongoing discussions about the disease as the child matures cognitively, emotionally, and sexually.

Whenever possible, disclosure should occur at a time when the child is clinically and emotionally stable and the caregiver is ready to disclose. Preferably, disclosure should not take place during an acute illness or family crisis and should not coincide with other events such as birthdays, holidays, or graduations. Disclosure can provide an opportunity for a family to share important information and to focus on health, communication, and relationships.

The disclosure process should not be rushed; however, the timing of disclosure becomes more pressing as the child nears adolescence, a time when the potential to engage in sexual and substance-using behavior may emerge (see Considerations for Disclosure to Perinatally Infected Adolescents).

References:
  1. American Academy of Pediatrics, Committee on Pediatric AIDS. Disclosure of illness status to children and adolescents with HIV infection. Pediatrics 1999;103:164-166. [PubMed]
  2. Blasini I, Chantry C, Cruz C, et al. Disclosure model for pediatric patients living with HIV in Puerto Rico: Design, implementation, and evaluation. J Dev Behav Pediatr 2004;25:181-189. [PubMed]

Collaborating with Families to Develop a Disclosure Plan

November 2009

RECOMMENDATIONS
  • Clinicians or a member of the multidisciplinary healthcare team should:
    • Assess, early in the patient’s childhood, the readiness of caregivers to disclose HIV diagnosis to their infected child (AIII)
    • Work with caregivers to develop a disclosure plan that meets the individualized needs of the family and the child (AIII)
  • Clinicians or a member of the multidisciplinary healthcare team should discuss the following with caregivers of HIV-infected children on an ongoing basis:
    • Caregivers’ concerns about disclosure (AIII)
    • The importance of ongoing communication with the child regarding health issues (AIII)
    • Benefits and risks of disclosing the diagnosis of HIV infection to the child (BIII)
    • The potential harm that can result from long-term nondisclosure (BIII)
  • These discussions should be documented in the child’s medical record.
  • When caregivers are reluctant to develop a disclosure plan, clinicians should ask about their concerns and attempt to develop a plan that addresses those concerns. Referrals for counseling and additional assistance regarding disclosure issues may be necessary. (AIII)
KEY POINT
Caregivers who are HIV-infected can provide a positive model of healthy behaviors for their children by tending to their own health needs, such as medication adherence and medical appointments.

Preparing caregivers to disclose HIV status to the infected child may take several months or even years [1]. Many caregivers with HIV infection have difficulty accepting the illness, either their own or their child’s, and struggle with whether or not to disclose the diagnosis of HIV infection. The following are common reasons why caregivers are reluctant to disclose HIV to their children [2]:

  • Fear that the infected child will inappropriately disclose his/her HIV status, especially in families in which the diagnosis remains closely guarded
  • Fear of stigma, rejection, and loss of support by the family/community
  • Desire to protect the child from worrying about his/her future
  • The possibility that the burden of learning of his/her HIV status will lead to depression or other mental health issues
  • Feelings of guilt and shame may prevent HIV-infected caregivers from disclosing their own infection to their child

Clinicians should respect caregivers’ reasons for fearing or resisting disclosure and should attempt to understand the factors associated with the reluctance to disclose. Validation of caregivers’ concerns can foster a partnership and prevent the development of an adversarial relationship between the members of the healthcare team and caregivers. Appendix B, Strategies to Facilitate Caregiver Readiness to Disclose, provides strategies that can be used to alleviate caregivers’ concerns regarding disclosure.

Motivational interviewing may be useful for facilitating discussions with caregivers who are not ready to disclose HIV to their child [3]. In a motivational interviewing framework, clinicians adjust the tenor of their discussions to fit the caregivers’ current readiness and encourage caregivers to discuss all of their feelings and concerns about disclosure (both pros and cons), as well as their long-term goals for the physical and emotional well-being of their child. The motivation to disclose is then framed in the context of the caregivers’ values, and the caregivers gain confidence in their ability to create a disclosure plan that supports their child’s best interests. 

Partial disclosure may be an effective strategy to use to help caregivers who are not ready to use the terms “HIV” or “AIDS.” Partial disclosure involves teaching a child about his/her body and how the immune system works before using the actual words “HIV” or “AIDS.” Partial disclosure is useful for building a context in which HIV disclosure can be more meaningful for children. Within these parameters, clinicians can be honest with their patients without forcing disclosure before the caregivers are ready. Clinicians need to remain truthful in their communications with children about their illnesses so that they do not undermine the therapeutic relationship. Collusion with caregivers who are not truthful can be detrimental for some children because they may ultimately feel betrayed by the adults they trusted.

In some cases, caregivers and providers may require additional support to inform children/adolescents of their HIV status. In these cases, referral to a “disclosure specialist” or mental health professional who is experienced with discussing disclosure issues should be considered.

References:
  1. Nehring W, Lashley F, Malm K. Disclosing the diagnosis of pediatric HIV infection: Mothers’ views. J Soc Pediatr Nurs 2000;5:5-14. [PubMed]
  2. Lesch A, Swartz L, Kagee A, et al. Paediatric HIV/AIDS disclosure: Towards a developmental and process-oriented approach, AIDS Care 2007;19:811-816. Available at: http://dx.doi.org/10.1080/09540120601129301
  3. Britt E, Hudson SM, Blampied NM. Motivational interviewing: A review. Patient Educ Couns 2004;53:147-155. [PubMed]

Individualizing the Disclosure Plan

November 2009

RECOMMENDATION
  • Clinicians should work with caregivers to develop an individualized disclosure plan that addresses each family’s unique circumstances. (AIII)

Below is a list of factors that should be discussed with the caregiver when developing an individualized disclosure plan. Circumstances that may require additional consideration and support include adopted children who do not yet know their adoptive status and children with non-infected siblings.

Factors to Consider When Developing an Individualized Disclosure Plan

  • Child’s age, cognitive ability, and developmental understanding of illness and mortality: Developmentally appropriate words and explanations should be used to maximize the child’s understanding of the disease and diagnosis (see Preparing for the Disclosure Discussion).
  • What the child has already been told and already knows about medications or doctor visits: Provides a starting point for the disclosure discussion. Some older children may already know or suspect they are HIV-infected.
  • Clinical status of child: Symptomatic and asymptomatic children usually have a different understanding of the disease.
  • Other disclosures that may need to be made, such as adoptive status, paternity issues, or parental HIV diagnosis: Child may need additional time and support to cope with these factors before HIV disclosure is made.
  • Caregivers’ thoughts about disclosure: Caregivers’ readiness to disclose may affect the timing of disclosure and will guide caregiver-clinician discussions regarding disclosure.
  • Cultural influences: Cultural beliefs regarding child rearing, health, illness, and death should be discussed and respected to encourage a supportive partnership.
  • Family/social circumstances: Whether a child is adopted or in foster care, has siblings, and/or if siblings are HIV-infected may affect the approach to disclosure.
  • Anticipated response of the child when learning his/her diagnosis: Children who are emotionally unstable or who have poor coping skills may require closer post-disclosure follow-up and additional support.
  • Types of support available to the child and family once disclosure occurs, such as counseling and peer support groups: A post-disclosure plan for assessment and support should be in place before disclosure occurs.

Disclosing Both Adoptive Status and HIV Diagnosis

RECOMMENDATION
  • Consultation with or referral to a mental health professional should be considered when working with caregivers who are disclosing both adoptive status and HIV diagnosis to the child. (BIII)

Providers and caregivers may need to address different issues with HIV-infected children who are in foster care or are adopted. Some of these children may not understand why they are infected but their caregivers are not. Before disclosing HIV diagnosis to these children, they need to know that they were adopted and how HIV transmission occurs.

Children who have experienced the death of one or both biological parents need time to grieve and adapt to their adoptive caregivers before disclosure takes place. The healthcare team should recognize that for these children there may be an absence of stable, consistent, and supportive relationships with adults.

Effects of Disclosure on Siblings

RECOMMENDATION
  • Clinicians or a member of the healthcare team should collaborate with caregivers about the timing and effect of disclosure on both HIV-infected and non-HIV-infected siblings. (BIII)

As part of the disclosure plan, the clinician or member of the healthcare team should collaborate with the caregiver to discuss disclosure of a child’s HIV status to non-infected and infected siblings in a developmentally appropriate manner. Ideally, the disclosure process will lead to greater support for the HIV-infected child within his/her family.

An older sibling who is also HIV-infected may be able to provide extra support to the younger infected child by discussing his/her own thoughts, emotions, and experiences as someone living with HIV. More mature non-infected siblings who know the serostatus of the infected child may become additional sources of support for both the infected sibling and other family members. However, some non-infected siblings may feel neglected or become jealous of their HIV-infected sibling because of the attention that the “sick” child receives. Non-infected siblings need ongoing support and validation to meet their own emotional needs and may require referral to mental health services.

Considerations for Disclosure to Perinatally Infected Adolescents

November 2009

RECOMMENDATIONS
  • Clinicians should:
    • Strive to ensure that, within a reasonable time frame, HIV-infected adolescents are fully informed of their HIV status (AIII)
    • Assess what adolescents understand about their health/illness and use that information to guide future discussions and the disclosure process (AIII)
    • Give adolescents the opportunity to discuss their health/illness and ask questions independent of caregivers (AIII)
    • Help the adolescent identify a supportive person to whom he/she can safely disclose and discuss HIV-related issues (BIII)
    • Incorporate discussions about disclosure and understanding of the illness into routine ongoing care (AIII)
    • Counsel about sexuality and risk-reduction behaviors (AIII)
  • Caregivers who object to disclosing an adolescent’s HIV diagnosis should receive intensive support and services from the clinical team to address their concerns. (AIII)
  • Decisions regarding disclosure to adolescents with significant cognitive deficits need to be individualized. Specific strategies should be undertaken based on adolescent development. (AIII)

Disclosure and knowledge of HIV status are essential components in the care of perinatally infected adolescents. Nondisclosure of HIV status reinforces stigma, fosters secrecy, and prevents the individual from assuming responsibility for their own health care and well-being. Nondisclosure also places adolescents who are sexually active at risk for unknowingly exposing others to HIV. Because of the significant consequences that nondisclosure may have for perinatally infected adolescents, this Committee feels that disclosure should occur before adolescence and supports the AAP recommendation that:

Adolescents should know their HIV status. They should be fully informed to appreciate consequences for many aspects of their health, including sexual behavior. Adolescents also should be informed of their HIV status to make appropriate decisions about treatment and participation in clinical treatment trials. Physicians should also encourage adolescents to involve their parents in their care [1].

In New York State, caregiver consent is required for clinicians to treat minors for HIV/AIDS (exceptions, including minors who are married and minors who are pregnant or parenting, have been described elsewhere [2,3]); however, adolescents should actively participate in their own care and treatment decisions. Without knowing their HIV status, adolescents are unable to make informed decisions. Knowledge of HIV status will likely affect medication adherence and how the clinician counsels the patient about sexuality and risk-reduction.

Because a minor’s caregiver must consent to the minor’s HIV care, clinicians should not disclose HIV diagnosis to a minor without the caregiver’s consent. Refusal from the caregiver to give such consent may create opposing pressures on the clinician that may result in poor clinical outcomes. Clinicians should be aware of these potential conflicts and should arrange multidisciplinary case conferences to develop a plan for working with these families.

Assessing Adolescent Patients’ Understanding of Their Health

The disclosure process for adolescents should start with an assessment of the adolescent’s knowledge about his/her illness. Adolescents should be asked about their understanding of their medications, their illness, and reasons for their doctors’ visits. The information the adolescent provides should be used to guide future dialogue about both disclosure and the adolescent’s health. Some adolescents may already know or suspect they are HIV-infected even though their caregivers and medical team have not referred to HIV by its actual name.

Providing Opportunities for Adolescents to Discuss HIV Diagnosis

All HIV-infected adolescents should be given the opportunity to discuss their health with the clinician and healthcare team and should be given the choice of speaking to their providers with or without their caregivers. Some young adolescents may prefer to have their caregiver(s) present during discussions.

Speaking with a member of the healthcare team independent of the caregiver should be encouraged to:

  • build a trusting therapeutic relationship between clinician and patient
  • allow adolescents to more easily discuss topics that may be difficult to discuss with a caregiver present
  • develop self-management skills

Open discussion about the disease can provide an opportunity to address false or negative ideas that the adolescent may have about issues such as transmission, treatment, life expectancy, or reproductive options. Such discussions can also serve as opportunities for risk-reduction counseling, including standard precautions and safe-sex responsibilities.

Clinicians should help HIV-infected adolescents identify a supportive person(s) with whom they can safely discuss HIV-related issues. Some may identify a supportive adult family member, a member of the clinical team, or a peer. Peer support groups for HIV-infected adolescents can provide positive experiences that promote a sense of normalcy, lessen anxiety, and improve self-esteem.

Close post-disclosure follow-up is necessary to ensure that the adolescent is receiving the support that he/she may need (see Post-Disclosure Assessments).

References:
  1. American Academy of Pediatrics, Committee on Pediatric AIDS. Disclosure of illness status to children and adolescents with HIV infection. Pediatrics 1999;103:164-166. [PubMed]
  2. New York Public Health Law Section § 2504. Enabling Certain Persons To Consent For Certain Medical, Dental, Health And Hospital Services. Available at: http://law.onecle.com/new-york/public-health/PBH02504_2504.html
  3. Feierman J, Lieberman D, Schissel A, et al. Teenagers, Health Care & the Law. A guide to the law on minors’ rights in New York State. New York, New York: New York Civil Liberties Union (NYCLU) Reproductive Rights Project; 2002.

Preparing for the Disclosure Discussion

November 2009

RECOMMENDATIONS
  • Clinicians should educate caregivers about using developmentally appropriate words and language when disclosing HIV diagnosis to an infected child. (AIII)
  • Prior to disclosure, the clinician or a member of the healthcare team should assess the child’s coping skills, family and peer support, school/work functioning, and interests. (AIII)

Caregivers should be able to choose the disclosure strategies that suit them best, such as whether they want to disclose the diagnosis independently or together with a member(s) of the healthcare team. If caregivers want the healthcare team to participate in the disclosure discussion, a separate appointment devoted only to disclosure may provide the opportunity for a more thorough and honest discussion with the infected child. Follow-up appointments and calls are necessary to help assess the need for additional support and to continue the disclosure process over time (see Post-Disclosure Assessments).

When helping families disclose HIV diagnosis to the infected adolescent, the clinician or a member of the healthcare team should explain that the use of developmentally appropriate words and explanations is the most effective and comprehensible approach to the adolescent’s understanding of the disease and diagnosis. The words and terms that are used can gradually evolve into more HIV-specific language and concepts about immune status or health. Clear and developmentally appropriate explanations of the diagnosis and disease need to be reinforced and repeated as the adolescent matures.

Strategies for Disclosing Based on Developmental Stage (Formal Operational) [1]

  • Use visual aids such as books or websites to demonstrate the key concepts in HIV, the immune system, and illness
  • Use slightly more complex language to convey the interactions between health, illness, and treatment
  • Use examples such as, “Your body has different parts and your immune system helps to protect your body from infections. HIV virus is a type of infection that destroys your immune system’s T helper cells. Your medications can help to stop the HIV virus from hurting your T helper cells and immune system.”
  • Discuss and explore issues regarding HIV transmission using examples of age-appropriate behaviors
  • Discuss issues related to privacy, stigma, and confidentiality
  • Explore normal sexual development and education

General Principles for Disclosing HIV Status: [2]

  • Date of disclosure should not coincide with other events such as birthdays, holidays, graduation, etc.
  • Use clear and developmentally appropriate explanations of the disease/diagnosis
  • Share the diagnosis quickly, do not delay or stall
  • Promote sharing of feelings, but also accept silence
  • Always allow the child to ask questions
  • Give developmentally appropriate educational materials
  • Both the healthcare team and caregivers should be involved throughout the process
  • Pre-disclosure assessment of the following areas of the child’s or adolescent’s functioning will provide a baseline from which the impact of the disclosure can be monitored post-disclosure:
  • The child’s school functioning
  • Family and peer relationships and support
  • Interests and activities
  • Mood and behavior
References:
  1. Lesch A, Swartz L, Kagee A, et al. Paediatric HIV/AIDS disclosure: Towards a developmental and process-oriented approach, AIDS Care 2007;19:811-816. Available at: http://dx.doi.org/10.1080/09540120601129301
  2. Blasini I, Chantry C, Cruz C, et al. Disclosure model for pediatric patients living with HIV in Puerto Rico: Design, implementation, and evaluation. J Dev Behav Pediatr 2004;25:181-189. [PubMed]

Post-Disclosure Assessments

November 2009

RECOMMENDATIONS
  • The clinician or a member of the healthcare team should assess the child/adolescent’s emotional well-being and functioning at every visit after disclosure of HIV diagnosis has occurred. The following areas of functioning should be assessed: (AIII)
    • School functioning
    • Family and peer relationships and support
    • Interests and activities
    • Mood and behavior
  • The clinician should work closely with caregivers to monitor the child for changes in functioning that may signify poor adjustment. (AIII)
  • Clinicians should refer children who demonstrate significant post-disclosure changes in behavior for additional support. (AIII)
  • The healthcare team should provide all disclosed HIV-infected children and their families with ongoing support through the adjustment of learning to live with HIV infection. (AIII)

Disclosure is a process that does not end with telling an HIV-infected child the name of their illness or diagnosis. After the HIV diagnosis has been disclosed to the infected child, follow-up calls and visits are needed to monitor the child and family’s understanding of the illness and their emotional and psychological adjustment. Evaluating the child/adolescent pre- and post-disclosure may help the healthcare team and families identify children who require additional support and services. Some children who learn of their HIV status may experience guilt and shame and may isolate themselves as a result of the stigma and secrecy surrounding the disease. Changes in behavior and school functioning may occur in these children and may be symptoms of depression. Patients and families who have a difficult adjustment to HIV disclosure without progress over time should be referred for mental health services and additional support.

Separate discussions with family members and children may be necessary so that clinicians can address the unique issues of each family member in a safe and supportive environment. Adolescents and their families should be made aware of support resources that are available within their programs or communities.

All Recommendations

Subcommittee on the Care of Adolescents with HIV Infection, November 2009

ALL RECOMMENDATIONS: DISCLOSURE OF HIV TO PERINATALLY INFECTED ADOLESCENTS
Introduction
  • Clinicians and other members of the multidisciplinary team should collaborate with caregivers of HIV-infected children to disclose the diagnosis of HIV to the child in a developmentally appropriate manner. (AIII)
When Should the Disclosure Process Begin?
  • Ongoing dialogue between the clinical team and caregivers regarding disclosure of HIV diagnosis and health concepts should occur early in the patient’s childhood. (AIII)
Collaborating with Families to Develop a Disclosure Plan 
  • Clinicians or a member of the multidisciplinary healthcare team should:
    • Assess, early in the patient’s childhood, the readiness of caregivers to disclose HIV diagnosis to their infected child (AIII)
    • Work with caregivers to develop a disclosure plan that meets the individualized needs of the family and the child (AIII)
  • Clinicians or a member of the multidisciplinary healthcare team should discuss the following with caregivers of HIV-infected children on an ongoing basis:
    • Caregivers’ concerns about disclosure (AIII)
    • The importance of ongoing communication with the child regarding health issues (AIII)
    • Benefits and risks of disclosing the diagnosis of HIV infection to the child (BIII)
    • The potential harm that can result from long-term nondisclosure (BIII)
  • These discussions should be documented in the child’s medical record.
  • When caregivers are reluctant to develop a disclosure plan, clinicians should ask about their concerns and attempt to develop a plan that addresses those concerns. Referrals for counseling and additional assistance regarding disclosure issues may be necessary. (AIII)
Individualizing the Disclosure Plan 
  • Clinicians should work with caregivers to develop an individualized disclosure plan that addresses each family’s unique circumstances. (AIII)
  • Consultation with or referral to a mental health professional should be considered when working with caregivers who are disclosing both adoptive status and HIV diagnosis to the child. (BIII)
  • Clinicians or a member of the healthcare team should collaborate with caregivers about the timing and effect of disclosure on both HIV-infected and non-HIV-infected siblings. (BIII)
Preparing for the Disclosure Discussion 
  • Clinicians should educate caregivers about using developmentally appropriate words and language when disclosing HIV diagnosis to an infected child. (AIII)
  • Prior to disclosure, the clinician or a member of the healthcare team should assess the child’s coping skills, family and peer support, school/work functioning, and interests. (AIII)
Considerations for Disclosure to Perinatally-Infected Adolescents 
  • Clinicians should:
    • Strive to ensure that, within a reasonable time frame, HIV-infected adolescents are fully informed of their HIV status (AIII)
    • Assess what adolescents understand about their health/illness and use that information to guide future discussions and the disclosure process (AIII)
    • Give adolescents the opportunity to discuss their health/illness and ask questions independent of caregivers (AIII)
    • Help the adolescent identify a supportive person to whom he/she can safely disclose and discuss HIV-related issues (BIII)
    • Incorporate discussions about disclosure and understanding of the illness into routine ongoing care (AIII)
    • Counsel about sexuality and risk-reduction behaviors. 
  • Caregivers who object to disclosing an adolescent’s HIV diagnosis should receive intensive support and services from the clinical team to address their concerns. (AIII)
  • Decisions regarding disclosure to adolescents with significant cognitive deficits need to be individualized. Specific strategies should be undertaken based on the developmental stage of the adolescent. (AIII)
Post-Disclosure Assessments 
  • The clinician or a member of the healthcare team should assess the child/adolescent’s emotional well-being and functioning at every visit after disclosure of HIV diagnosis has occurred. The following areas of functioning should be assessed: (AIII)
    • School functioning
    • Family and peer relationships and support
    • Interests and activities
    • Mood and behavior
  • The clinician should work closely with caregivers to monitor the child for changes in functioning that may signify poor adjustment. (AIII)
  • Clinicians should refer children who demonstrate significant post-disclosure changes in behavior for additional support. (AIII)
  • The healthcare team should provide all disclosed HIV-infected children and their families with ongoing support through the adjustment of learning to live with HIV infection. (AIII)

Transition to Adult Care Guideline

Introduction

Subcommittee on the Care of Adolescents with HIV Infection, June 2011

As HIV-infected adolescents grow into adulthood, it becomes necessary for them to transfer to adult care settings and take responsibility for their own health and disease management. Transition in this setting can be defined as “a multifaceted, active process that attends to the medical, psychosocial, and academic or vocational needs of adolescents as they move from the child- to the adult-focused healthcare system. Health care transition should also facilitate transition in other areas of life as well (e.g., work, community, and school)” [1].

Adolescents and young adults are an increasing proportion of the HIV-infected population. In 2008, 17.6% of new HIV cases in New York State were in the 13- to 24-year-old age group. In addition, more perinatally infected patients have entered this age group. The HIV-infected adolescent population comprises a mixed group of 1) perinatally infected adolescents who are now surviving into adulthood, and 2) behaviorally infected adolescents, most of whom were infected sexually. Despite sharing some common characteristics, these two populations are quite distinct with respect to their needs and challenges.

The American Academy of Pediatrics defines adolescence as 13 to 21 years of age. The recommendations in this chapter pertain to both adolescents and young adults because many pediatric and adolescent clinicians follow HIV-infected patients from 13 to 24 years of age. 

Purpose of this guideline: This guideline has been developed to assist providers with the transition process to ensure that HIV-infected young adults are successfully and seamlessly integrated into an adult care setting. Recommendations are meant to serve as a guide and will need to be tailored to the individual patient.

General principles: The cornerstones of effective transitioning that are addressed in this guideline are listed below.

  • Individualize the approach used
  • Identify adult care providers who are willing to care for adolescents and young adults
  • Begin the transition process early and ensure communication between the pediatric/adolescent and adult care providers prior to and during transition
  • Develop and follow an individualized transition plan for the patient in the pediatric/adolescent clinic; develop and follow an orientation plan in the adult clinic. Plans should be flexible to meet the adolescent’s needs
  • Use a multidisciplinary transition team, which may include peers who are in the process of transitioning or who have transitioned successfully
  • Address comprehensive care needs as part of transition, including medical, psychosocial, and financial aspects of transitioning
  • Allow adolescents to express their opinions
  • Educate HIV care teams and staff about transitioning

Challenges and Barriers

Common barriers have been identified in the literature regarding transition of adolescents with chronic diseases into adult care [2-14]. Many young patients experience worry and anxiety about transitioning and have a difficult time adjusting to the increased responsibility and expectations in an adult care setting [15-17]. Issues specific to HIV-infected youth may make the transition more difficult for this population compared with adolescents with other chronic illnesses [18].

Transition to an adult care setting is a challenge for most HIV-infected adolescent patients because of the loss of the stable and long-term nature of their relationships with their pediatric or adolescent healthcare team [19]. HIV-infected adolescents who have lost family members or are estranged from their families may feel that their pediatric or adolescent care providers have become their primary support system. Transitioning to an adult care setting abruptly or without preparation may result in the patient withdrawing from medical care altogether because the adolescent is left feeling “dumped” or abandoned, which may further exacerbate a perception of overall loss.

Appendix A: Challenges to Successful Transitioning, lists common challenges of transition, HIV-specific challenges, and challenges specific to both perinatally and behaviorally infected adolescents.

RESOURCES
References:
  1. Reiss J, Gibson R. Health care transition: Destinations unknown. Pediatrics 2002;110:1307-1314. [PubMed]
  2. Bolton-Maggs PH. Transition of care from paediatric to adult services in haematology. Arch Dis Child 2007;92:797-801. [PubMed]
  3. Soanes C, Timmons S. Improving transition: A qualitative study examining the attitudes of young people with chronic illness transferring to adult care.J Child Health Care 2004;8:102-112. [PubMed]
  4. Weissberg-Benchell J, Wolpert H, Anderson BJ. Transitioning from pediatric to adult care: A new approach to the post-adolescent young person with type 1 diabetes. Diabetes Care 2007;30:2441-2446. [PubMed]
  5. Scal P. Transition for youth with chronic conditions: Primary care physicians’ approaches. Pediatrics 2002;110:1315-1321. [PubMed]
  6. Higgins SS, Tong E. Transitioning adolescents with congenital heart disease into adult health care. Prog Cardiovasc Nurs 2003;18:93-98. [PubMed]
  7. Beresford B. On the road to nowhere? Young disabled people and transition. Child Care Health Dev 2004;30:581-587. [PubMed]
  8. Hewer SC, Tyrrell J. Cystic fibrosis and the transition to adult health services. Arch Dis Child 2008;93:817-821. [PubMed]
  9. Flume PA, Taylor LA, Anderson DL, et al. Transition programs in cystic fibrosis centers: Perceptions of team members. Pediatr Pulmonol 2004;37:4-7. [PubMed]
  10. Hink H, Schellhase D. Transitioning families to adult cystic fibrosis care. J Spec Pediatr Nurs 2006;11:260-263. [PubMed]
  11. Wallis C. Transition of care in children with chronic disease. BMJ 2007;334:1231-1232. [PubMed]
  12. Pacaud D, Yale J-F, Stephure D, et al. Problems in transition from pediatric care to adult care for individuals with diabetes. Can J Diabetes2005;29:13-18.
  13. Cameron JS. The continued care of children with renal disease into adult life. Pediatr Nephrol 2001;16:680-685. [PubMed]
  14. Chira P, Sandborg C. Adolescent rheumatology transitional care: Steps to bringing health policy into practice. Rheumatology 2004;43:687-689. [PubMed]
  15. Miles K, Edwards S, Clapson M. Transition from pediatric to adult services: Experiences of HIV-positive adolescents. AIDS Care 2004;16:305-314. [PubMed]
  16. Wiener LS, Zobel M, Battles H, et al. Transition from a pediatric HIV intramural clinical research program to adolescent and adult community-based care services: Assessing transition readiness. Soc Work Health Care 2007;46:1-19. [PubMed]
  17. Valenzuela JM, Buchanan CL, Radcliffe J, et al. Transition to adult services among behaviorally infected adolescents with HIV: A qualitative study. J Pediatr Psychol 2011;36:134-140. [PubMed]
  18. Cervia JS. Transitioning HIV-infected children to adult care. J Pediatr 2007;150:E1. [PubMed]
  19. Catallozzi M, Futterman DC. HIV in adolescents. Curr Infect Dis Rep 2005;7:401-405. [PubMed]

Reference:

Transition Preparation in the Pediatric/Adolescent Care Setting

June 2011

RECOMMENDATION
  • The pediatric/adolescent care provider should:
    • Develop a transition plan several years prior to transition and update it at regular intervals (AIII)
    • Ensure that HIV-infected youth understand their chronic illness and its management, and provide them with skills to negotiate care in an adult clinic setting (see text) (AIII)
    • Assess patients, in an individualized manner, for development of sufficient skills and understanding for successful transition (AIII)
    • Address the individual barriers for each patient that may be preventing him/her from acquiring skills, such as developmental delays, anxiety, post-traumatic stress disorder, transient living conditions (AIII)
    • Prepare and discuss a current medical history with the patient so that he/she is aware of previous hospitalizations or allergies that may have occurred during infancy or childhood (AIII)

Developing a Transition Plan

RECOMMENDATIONS
  • The pediatric or adolescent care provider should collaborate with the patient and family to develop a transition plan that spans several years with concrete goals and a timeline. Whenever possible, a written transition plan should be developed at least 3 years before the transition is planned and should be updated at least annually. (AIII)
  • For adolescents who do not yet know their HIV status, disclosure should be a primary goal of the transition plan. (AIII)
  • As part of the transition plan, arrangements should be made for transitioning patients to meet their new providers well in advance of their final appointment with their pediatric or adolescent primary care provider. (AIII)

It is recommended that providers plan to take at least 3 years to prepare patients for the transition to an adult practice setting. The transition plan, together with individual goals and achievements, should be reviewed and modified annually.

RESOURCES

The following resources contain examples of transition tools for individual facilities to develop for their own use. Click the link to download a sample in PDF.

*Sample forms 1–3 adapted, with permission, from Jacob S, Jearld S. Transitioning Your HIV+ Youth to Healthy Adulthood: A Guide for Health Care Providers. Children’s Hope Foundation, Partnership for Family Health, and Bellevue Hospital Center, New York City Health and Hospitals Corporation. April 2007.

There are unique clinical considerations that should be considered when developing transition plans for perinatally infected adolescents (see below). Disclosure of HIV status is a prerequisite for transition to adult care. For guidelines on disclosure, see Disclosure of HIV to Perinatally Infected Children and Adolescents.

Clinical considerations in perinatally infected adolescents:

  • More likely to be in advanced stages of HIV disease and immunosuppression
  • More likely to have history of opportunistic infections (OIs) with complications
  • Antiretroviral therapy (ART) is more likely to be necessary to control viremia and increase CD4 counts
  • More complicated ART regimens
  • More likely to have multidrug resistant virus and heavy antiretroviral exposure history
  • More complicated non-antiretroviral medications, such as OI prophylaxis and treatment
  • Greater obstacles to achieving functional autonomy due to physical and developmental disabilities/greater dependency on family
  • When pregnant, higher risk of complications due to more advanced disease and higher risk of second-generation HIV transmission due to multiple-drug resistance
  • Suboptimal immune response to immunizations and boosters

Clinical considerations in behaviorally infected adolescents:

  • More likely to be in earlier stages of HIV disease
  • Fewer OI complications
  • More likely to have higher CD4 counts*
  • When ART is initiated, simpler regimens can be used
  • Less likely to be resistant to antiretroviral drugs
  • Fewer developmental delays than in perinatal group, which may improve treatment adherence
  • More likely to achieve functional autonomy

*See Antiretroviral Therapy > When to Initiate ART.

Education and Skills Training for Adolescent Patients

RECOMMENDATIONS
  • The pediatric or adolescent care provider should offer training and practice in the specific skills that the patient will need in the adult clinic setting and should evaluate the patient’s progress toward these goals (see text). (AIII)
  • The pediatric or adolescent care provider should ensure that HIV-infected youth understand their chronic illness and its management. (AIII)

Patients cannot self-manage a chronic illness when they do not understand what the illness is. They should understand the basic biology of HIV, why their medications and treatments are necessary, and how to prevent transmission. Informed decision-making is the key to mature self-care and is the overall goal for successful transitioning.

The necessary skills for adolescents to engage successfully in adult care are listed below. Acquisition of these skills will help patients develop the ability to manage appointments, identify new symptoms, obtain medication refills, and properly use medical insurance.

Pediatric/adolescent healthcare systems are usually more flexible with adolescent patients regarding clinic policies. For example, pediatric/adolescent clinics will often accommodate patients who arrive late for appointments or who do not have appointments scheduled. However, the pediatric/adolescent care team should plan to implement a more structured appointment system prior to transition to promote skills building and to minimize “culture shock” or feelings of abandonment in the adult program, where policies are generally followed more strictly. Some adolescent programs use peer support groups for skills training and also have skills practice sessions with medical students and residents.

Skills to assist adolescents in achieving successful transition to an adult clinic: Ideally, the adolescent should be able to do the following before transitioning:

  • Know when to seek medical care for symptoms or emergencies
  • Identify symptoms and describe them
  • Make, cancel, and reschedule appointments
  • Arrive to appointments on time
  • Call ahead of time for urgent visits
  • Request prescription refills correctly and allow enough time for refills to be processed before medications run out
  • Negotiate multiple providers and subspecialty visits
  • Understand the importance of health insurance, how to select an appropriate healthcare plan, and how to obtain it and renew it
  • Understand entitlements and know how to access them
  • Establish a good working relationship with a case manager at the pediatric/adolescent site, which will enable the adolescent to work effectively with the case manager at the adult site

 

Identifying the Adult Care Provider

June 2011

RECOMMENDATION
  • The referring provider should identify an adult care provider or multidisciplinary team that:
    • Is experienced with caring for transitioning HIV-infected adolescents and young adults (AIII)
    • Is willing to engage in direct communication with the referring provider about the patient (AIII)
    • Accepts the patient’s health insurance (AIII)

Internists and infectious disease specialists who provide adult care generally are not experienced with pediatric and adolescent developmental issues or may be averse to dealing with the behavioral issues and multiple losses that many HIV-infected adolescents face. Locating a family or hospital-based medical practice that has experience with younger patients or is willing to develop appropriate skills and knowledge may help maintain transitioning patients in care. Adult care providers who are accepting care of HIV-infected youth for the first time should work with adolescent or pediatric providers who are experienced with transitioning when developing the transition plan.

When possible, the pediatric/adolescent healthcare team should assist the adolescent in choosing an adult clinic that best suits the individual. For example, patients with comorbidities, such as hepatitis C virus co-infection, diabetes, or mental health disorders, need to be in a setting that can provide comprehensive care. Some adolescents may feel that location is the most important factor due to time and transportation restrictions. Lesbian, gay, bisexual, and transgender (LGBT) youth may be looking for an environment that is “gay-friendly.”

In some pediatric/adolescent settings, it may be possible to include a family practitioner or an adult provider who divides his/her time between the adolescent and adult clinic. The adult provider then becomes a familiar member of the multidisciplinary team prior to transition.

RECOMMENDATIONS
  • HIV care should be provided in settings where patients can receive all services in one location from a multidisciplinary team. If a multidisciplinary team is not available, mental health and psychosocial support services should be available onsite or in an easily accessible location. The primary care team should be responsible for maintaining an ongoing plan for coordination of care among all service providers. (AIII)
  • In areas where comprehensive HIV services are not available, the patient should be referred to a primary care provider with experience in providing HIV care in addition to a provider experienced with ART management. The primary care provider should help the transitioning patient navigate the adult subspecialty clinic model. (AIII)
  • If gynecologic services are not available as part of a comprehensive care model in the adult HIV care program, the primary care provider should refer HIV-infected adolescents/young women to a gynecologist with expertise in counseling adolescents regarding reproductive health and perinatal transmission. (AIII)
  • The primary care provider and members of the multidisciplinary team also should be able to provide ongoing HIV transmission and risk-reduction counseling to adolescents. (AI)

Importance of a multidisciplinary approach: Many HIV-infected adolescents and young adults need access to complex mental health, alcohol and substance use, and psychosocial services. Unusually high rates of mental health diagnoses have been observed in both perinatally and behaviorally infected adolescent clinic cohorts [1-6].

The primary care provider and members of the multidisciplinary team also should be able to provide ongoing HIV transmission and risk-reduction counseling to adolescents [7]. Ideally, an adult care provider who does not work with a multidisciplinary team should have access to necessary supportive services onsite or nearby. If patients need to be referred to other facilities for services, the primary care team should be responsible for maintaining an ongoing plan for coordination of care among all service providers. All providers involved in the patient’s care are then aware of care plans from other providers, and staff can then follow up with patients when appointments are missed.

KEY POINT
When care is complex or fragmented, assignment of a specific staff person, such as a nurse, case manager, or social worker, to a coordinating role is important to ensure that a comprehensive and effective management plan is implemented that includes optimal support and follow-up.

Onsite gynecological services, provided by either the primary care provider, a nurse practitioner, gynecologist, or nurse midwife with HIV expertise, is the best model to ensure adherence to gynecologic care. If the patient is referred to a general gynecologic service, the primary care provider needs to ensure that topics specific to HIV care, such as drug interactions between antiretroviral agents and hormonal contraceptives and “dual protection” education (consistent use of a reliable contraceptive method in addition to condoms used to prevent HIV transmission) are addressed (see Care of Female Adolescents with HIV-Infection and Contraception for HIV-Infected Women).

References:
  1. Mellins CA, Brackis-Cott E, Dolezal C, et al. Psychiatric disorders in youth with perinatally acquired human immunodeficiency virus infection.Pediatr Infect Dis J 2006;25:432-437. [PubMed]
  2. Mellins CA. Brackis-Cott E, Leu CS, et al. Rates and types of psychiatric disorders in perinatally human immunodeficiency virus-infected youth and seroreverters. J Child Psychol Psychiatry 2009;50:1131-1138. [PubMed]
  3. Murphy DA, Moscicki AB, Vermund SH, et al. Psychological distress among HIV(+) adolescents in the REACH study: Effects of life stress, social support, and coping. The Adolescent Medicine HIV/AIDS Research Network. J Adolesc Health 2000;27:391-398. [PubMed]
  4. Radcliffe J, Fleischer CL, Hawkins LA, et al. Posttraumatic stress and trauma history in adolescents and young adults with HIV. AIDS Patient Care STDs 2007;21:501-508. [PubMed]
  5. Gaughan DM, Hughes MD, Oleske JM, et al. Psychiatric hospitalizations among children and youths with human immunodeficiency virus infection.Pediatrics 2004;113:e544-e551. [PubMed]
  6. Scharko AM. DSM psychiatric disorders in the context of pediatric HIV/AIDS. AIDS Care 2006;18:441-445. [PubMed]
  7. Fisher JD, Fisher WA, Cornman DH, et al. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006;41:44-52. [PubMed]

Preparing for Transitioning Patients to the Adult Care Setting

June 2011

RECOMMENDATION
  • The adult care provider should:
    • Become knowledgeable regarding the challenges of transition for older adolescents and young adults to an adult care setting (AIII)
    • Prior to transition, learn from the referring provider the particular challenges and goals for the patient; consider how to continue building the adolescent’s skills (AIII)
    • Meet the patient, with or without family members, before the change in care (AIII)
    • Assign one clinic staff member as point person and have his/her contact information available, including hours when contact is possible (see Use of Transition Agent or Patient Advocate) (AIII)
    • Have an orientation plan in place to acquaint the newly transitioned patient to the new clinic environment (AIII)

The adult provider or multidisciplinary team should have a plan in place to orient newly transitioning adolescents or young adults to the adult clinical care program. The clinic and/or the provider’s expectations of the newly transitioned patient should be explained during or before the first visit. The policy for late arrivals and walk-ins should be clearly explained to the adolescent.

Implementing the Transition Plan

June 2011

RECOMMENDATION
  • The referring clinician or provider team should arrange the transitioning of all current and anticipated services, including medical, mental health, and substance use treatment if needed. Individualized psychosocial needs, such as housing, employment, education, insurance, home-based services, or transportation, should also be addressed at this time. (AIII)

When to Transition

RECOMMENDATIONS
  • The transition plan should be implemented when the patient:
    • Demonstrates understanding of his/her disease and its management (AIII)
    • Demonstrates the ability to make and keep appointments (AIII)
    • Knows when to seek medical care for symptoms or emergencies (AIII)
  • Whenever possible, transition should be implemented when the patient’s disease is clinically stable. (BIII)

Most HIV-infected adolescents transition to adult care between 22 and 24 years of age [1]. However, developmental stage and readiness for transition may be better indicators than chronological age for determining when transition should occur. Patients with developmental delays or a chaotic and unstable life may need more time to become ready to transition. Adolescents who demonstrate independence in making their own decisions and show responsibility for their own care may be ready sooner.

The likelihood for successful transition is increased when both the pediatric/adolescent healthcare team and adult healthcare team recognize the broad spectrum of readiness in transitioning patients, ranging from those who are near full autonomy to those for whom disorder and confusion are a daily experience. For example, the transition process for a college student with well-developed career goals will be vastly different than that for a patient who is often hospitalized, nonadherent with medications, and frequently in crisis both emotionally and behaviorally. The goals and challenges of transition, as well as the support that will be needed during the process, will be individualized for each patient.

Communication Between the Adolescent and the Adult Care Provider

RECOMMENDATION
  • The referring clinician should:
    • Compose a medical summary that highlights key issues for the individual patient and includes the patient’s medical, psychological, and social history (AIII)
    • Schedule a case conference prior to transition (AIII)

Although the adult medical model does not generally provide time for direct communication between referring and receiving providers or provider teams, coordination between these providers can moderate the “culture shock” for a patient moving from child-, adolescent-, or family-centered care to adult-centered care. Adolescent medicine experts underscore that, for effective transitioning, a written summary is necessary but not sufficient. Direct communication between providers is essential. When the pediatric or adolescent care team is informed about the orientation plan in the adult clinic, it allows them to provide the transitioning patient with realistic expectations and helps them to prepare the patient with the necessary skills for managing his/her care in the new setting.

Use of Transition Agent or Patient Advocate

RECOMMENDATIONS
  • The adolescent care provider should designate one member of the healthcare team to oversee transition planning and implementation at both the old and new provider locations. (AIII)
  • The adult care provider should also designate a point person who will oversee the transition and who the patient can contact with any questions or concerns. (AIII)

The adolescent care provider or team should designate one care provider to oversee transition planning and implementation. This may be the primary care provider or another team member, such as a social worker. The coordinator should have equal visibility in and access to the pediatric and adult clinics to demonstrate continuity to the patient.

In some programs, a peer advocate, who may be someone who has recently transitioned successfully, works with the patient to create and track progress on an individualized transition plan. Peer advocates may accompany patients to the initial adult medical appointments and then provide support while they gain the independence and confidence to attend subsequent appointments by themselves [2,3].

The adult care provider should designate a point person who the patient can call with any questions or concerns. The point person can guide the patient to appropriate services and also alert providers if there are any concerns. This may be someone different than the designated contact person for clinic patients. For example, it might be a social worker or counselor who is familiar with developmental issues for transitioning adolescents and young adults. A primary care provider may choose to be called directly, or there may be a particular nurse or other staff member who is especially adept at working with young patients.

Challenges for Pregnant Adolescents During Transition

RECOMMENDATIONS
  • Adolescent care providers should have referral agreements with obstetrical services that can provide prenatal care to HIV-infected females during transition and that offer prenatal support services. (AIII)
  • Pediatric and/or adolescent care providers should be able to provide individualized support and advocacy for pregnant teens who are unprepared for transition to obstetrical services. (AIII)
  • Adolescent care providers should consider remaining the primary care provider for the adolescent during pregnancy. (AIII)

Adolescent pregnancy is often unplanned and can interrupt the process of transition planning and skills training. As a result, the patient may be referred to an obstetrics clinic before she is ready and well-prepared for adult care. This is a time when active support is particularly important to ensure that a patient’s discomfort with receiving treatment from a new provider and clinic do not lead to interruption of either prenatal or HIV care. For recommendations regarding care for HIV infected pregnant adolescents, see Care of the Female Adolescent with HIV Infection.

References:
  1. Gilliam PP, Ellen JM, Leonard L, et al. Transition of adolescents with HIV to adult care: Characteristics and current practices of the Adolescent Trials Network for HIV/AIDS Interventions. J Assoc Nurses AIDS Care 2010; June [ePub ahead of print]. [PubMed]
  2. HRSA Care ACTION. Transitioning from Adolescent to Adult Care. June 2007. Available at: ftp://ftp.hrsa.gov/hab/june2007.pdf
  3. Maturo D, Powell A, Major-Wilson H, et al. Development of a protocol for transitioning adolescents with HIV infection to adult care. J Pediatr Health Care 2011;25:16-23. [PubMed]

Role of the Adult Care Provider During Transition

June 2011

RECOMMENDATION
  • The adult care provider or multidisciplinary team should:
    • Assign an appropriate clinic staff person to be the primary contact person for newly transitioned adolescents and
      young adult patients (AIII)
    • Have a plan for identifying and managing problems that could interfere with continuity of care (BIII)

Adult care providers and clinic staff need to be prepared for individual differences in maturity and ability to cope. Some of their young patients will initially require far more support and psychosocial intervention than is customary in adult care settings if they are to transition successfully. Others will have already learned the skills needed to negotiate the healthcare system, appointments, and prescriptions and are eager to become self-sufficient adults. These patients likely only need to be educated about what is expected of them as patients in the new adult care setting.

The adult medical model does not generally allow for the extra time that may be needed for patients who are still learning how to speak for themselves and make mature decisions. The adult care provider and healthcare team should strive to devise ways to provide adequate time for the patient during the transition adjustment period.

Clinicians should strive to have a nonjudgmental approach to patient communication, especially when discussing sexual behaviors. Adolescents/young adults often tend to disengage from care if they feel that they have been spoken to in a judgmental manner.

Adult programs generally have more policies than pediatric and adolescent clinics. Policies for late arrivals and walk-ins should be clearly explained to the adolescent; however, to the extent possible, adult programs should also attempt to be flexible to accommodate the frequently less predictable schedules of adolescents/young adults.

Post-Transition Evaluation

June 2011

Post-Transition Assessment by the Adult Care Provider Team

RECOMMENDATION
  • The adult care provider or team should devise a plan to achieve the following on an ongoing basis:
    • Assessment of whether an individual patient is adequately caring for his/her own health (AIII)
    • Assessment of barriers that the patient is facing, what support is needed, and who will provide this support (AIII)
    • Skills training and support, either through the multidisciplinary team in the clinic or by liaison with a mental health or psychosocial support provider (AIII)

Many adolescents and young adults transitioning to adult clinics will not have much experience in practicing the healthcare behaviors that often develop with maturity. The adult care provider should be alert to signs that a young patient needs additional support or skills training. Offering immediate support will reduce the risk of the patient withdrawing from care. Any one of the following behaviors may alert the clinician that the patient requires additional support and indicates a need to revise the individual’s transition plan:

  • Multiple missed appointments
  • Discontinuation of medications
  • Substance use or other behaviors suggestive of poor adjustment
  • Loss of entitlements
  • Unstable housing

Checklist for successful transition: The checklist below can be used to evaluate the success of the transition.

  • The patient has accepted his or her chronic illness and is oriented toward future goals and hopes, including long-term survival.
  • The patient has learned the skills needed to negotiate appointments and multiple providers in an adult practice setting.
  • The patient has achieved personal and medical independence and is able to assume responsibility for his or her treatment and participate in decision-making.
  • The referring provider is familiar with the new provider and practice setting, and direct communication about an individualized plan for the patient has taken place.
  • Mental health services have been transitioned at the same time as medical services.
  • Psychosocial needs are met and entitlements are in place (housing, health insurance, home care, transportation).
  • Life skills have been addressed (e.g., educational goals, job training, parenting).
  • The patient receives uninterrupted comprehensive medical care.

Follow-up From Adolescent or Pediatric Care Provider

RECOMMENDATION
  • If adolescents withdraw from care in the adult clinic and return to their previous pediatric/adolescent clinic, the adolescent care provider should be prepared to help the patient identify services that can provide increased support and should encourage re-engagement in adult medical care. (AIII)

After transitioning to an adult care setting, patients may continue to have contact with their pediatric/adolescent care team providers, which may reinforce a successful transition or may uncover potential pitfalls in maintaining ongoing care at the adult facility. Therefore, continued communication between adult and pediatric providers remains a crucial aspect of the transition process.

Both the patient’s and the pediatric/adolescent care provider’s desire to “check in” at the beginning of the transition process is part of normal and healthy closure and can mitigate the patient’s sense of loss. However, transitioning patients may continue to rely on their pediatric/adolescent care provider for emotional support. This provider should defer clinical management decisions to the new provider and should be alert to the risk of hindering the patient from establishing a trusting therapeutic relationship with his/her adult care provider.

Young patients who withdraw from care in an adult clinic will often return to their adolescent or pediatric provider. When this happens, the provider should be prepared to help the patient identify services that can provide increased support and should encourage re-engagement in adult medical care.

All Recommendations

Subcommittee on the Care of Adolescents with HIV Infection, June 2011

ALL RECOMMENDATIONS: TRANSITIONING HIV-INFECTED ADOLESCENTS INTO ADULT CARE
Preparing for Transition in the Pediatric/Adolescent Care Setting
  • The pediatric/adolescent care provider should:
    • Develop a transition plan several years prior to transition and update it at regular intervals (AIII)
    • Ensure that HIV-infected youth understand their chronic illness and its management, and provide them with skills to negotiate care in an adult clinic setting (see text) (AIII)
    • Assess patients, in an individualized manner, for development of sufficient skills and understanding for successful transition (AIII)
    • Address the individual barriers for each patient that may be preventing him/her from acquiring skills, such as developmental delays, anxiety, post-traumatic stress disorder, transient living conditions (AIII)
    • Prepare and discuss a current medical history with the patient so that he/she is aware of previous hospitalizations or allergies that may have occurred during infancy or childhood (AIII)
  • The pediatric or adolescent care provider should collaborate with the patient and family to develop a transition plan that spans several years with concrete goals and a timeline. Whenever possible, a written transition plan should be developed at least 3 years before the transition is planned and should be updated at least annually. (AIII)
  • For adolescents who do not yet know their HIV status, disclosure should be a primary goal of the transition plan. (AIII)
  • As part of the transition plan, arrangements should be made for transitioning patients to meet their new providers well in advance of their final appointment with their pediatric or adolescent primary care provider. (AIII)
  • The pediatric or adolescent care provider should offer training and practice in the specific skills that the patient will need in the adult clinic setting and should evaluate the patient’s progress toward these goals (see text). (AIII)
  • The pediatric or adolescent care provider should ensure that HIV-infected youth understand their chronic illness and its management. (AIII)
Identifying the Adult Care Provider
  • The referring provider should identify an adult care provider or multidisciplinary team that:
    • Is experienced with caring for transitioning HIV-infected adolescents and young adults (AIII)
    • Is willing to engage in direct communication with the referring provider about the patient (AIII)
    • Accepts the patient’s health insurance (AIII)
  • HIV care should be provided in settings where patients can receive all services in one location from a multidisciplinary team. If a multidisciplinary team is not available, mental health and psychosocial support services should be available onsite or in an easily accessible location. The primary care team should be responsible for maintaining an ongoing plan for coordination of care among all service providers. (AIII)
  • In areas where comprehensive HIV services are not available, the patient should be referred to a primary care provider with experience in providing HIV care in addition to a provider experienced with ART management. The primary care provider should help the transitioning patient navigate the adult subspecialty clinic model. (AIII)
  • If gynecologic services are not available as part of a comprehensive care model in the adult HIV care program, the primary care provider should refer HIV-infected adolescents/young women to a gynecologist with expertise in counseling adolescents regarding reproductive health and perinatal transmission. (AIII)
  • The primary care provider and members of the multidisciplinary team also should be able to provide ongoing HIV transmission and risk-reduction counseling to adolescents. (AI)
Preparing for Transitioning Patients to the Adult Care Setting 
  • The adult care provider should:
    • Become knowledgeable regarding the challenges of transition for older adolescents and young adults to an adult care setting (AIII)
    • Prior to transition, learn from the referring provider the particular challenges and goals for the patient; consider how to continue building the adolescent’s skills (AIII)
    • Meet the patient, with or without family members, before the change in care (AIII)
    • Assign one clinic staff member as point person and have his/her contact information available, including hours when contact is possible (AIII)
    • Have an orientation plan in place to acquaint the newly transitioned patient to the new clinic environment (AIII)
Implementing the Transition Plan 
  • The referring clinician or provider team should arrange the transitioning of all current and anticipated services, including medical, mental health, and substance use treatment if needed. Individualized psychosocial needs, such as housing, employment, education, insurance, home-based services, or transportation, should also be addressed at this time. (AIII)
  • The transition plan should be implemented when the patient:
    • Demonstrates understanding of his/her disease and its management (AIII)
    • Demonstrates the ability to make and keep appointments (AIII)
    • Knows when to seek medical care for symptoms or emergencies (AIII)
  • Whenever possible, transition should be implemented when the patient’s disease is clinically stable. (BIII)
  • The referring clinician should:
    • Compose a medical summary that highlights key issues for the individual patient and includes the patient’s medical, psychological, and social history (AIII)
    • Schedule a case conference prior to transition (AIII)
  • The adolescent care provider should designate one member of the healthcare team to oversee transition planning and implementation at both the old and new provider locations. (AIII)
  • The adult care provider should also designate a point person who will oversee the transition and who the patient can contact with any questions or concerns. (AIII)
  • Adolescent care providers should have referral agreements with obstetrical services that can provide prenatal care to HIV-infected females during transition and that offer prenatal support services. (AIII)
  • Pediatric and/or adolescent care providers should be able to provide individualized support and advocacy for pregnant teens who are unprepared for transition to obstetrical services. (AIII)
  • Adolescent care providers should consider remaining the primary care provider for the adolescent during pregnancy. (AIII)
Role of the Adult Care Provider During Transition 
  • The adult care provider or multidisciplinary team should:
    • Assign an appropriate clinic staff person to be the primary contact person for newly transitioned adolescents and
      young adult patients (AIII)
    • Have a plan for identifying and managing problems that could interfere with continuity of care (BIII)
Post-Transition Evaluation 
  • The adult care provider or team should devise a plan to achieve the following on an ongoing basis:
    • Assessment of whether an individual patient is adequately caring for his/her own health (AIII)
    • Assessment of barriers that the patient is facing, what support is needed, and who will provide this support (AIII)
    • Skills training and support, either through the multidisciplinary team in the clinic or by liaison with a mental health or psychosocial support provider (AIII)
  • If adolescents withdraw from care in the adult clinic and return to their previous pediatric/adolescent clinic, the adolescent care provider should be prepared to help the patient identify services that can provide increased support and should encourage re-engagement in adult medical care. (AIII)

Substance Use in Adolescents | with HIV Infection Guideline

Introduction

Subcommittee on the Care of Adolescents with HIV Infection, February 2009

RECOMMENDATIONS
  • Clinicians treating HIV-infected adolescents should know how to screen adolescents for substance use and, if substance misuse is present, to develop a treatment plan and make referrals as appropriate.
  • Clinicians should be familiar with the stages of substance use progression and patterns of adolescent drug and alcohol use.

The American Academy of Pediatrics defines adolescence as 13 to 21 years. However, many pediatric and adolescent clinicians follow patients from 13 to 24 years of age before they transition to adult HIV care. For the purpose of these guidelines, the term adolescents refers to both adolescents and young adults, 13 to 24 years of age.

The use and abuse of alcohol and other mood-altering substances can be particularly problematic for both adult and adolescent HIV-infected patients. However, substance use patterns are different between adolescents and adults [1]. Screening, assessment, and treatment of substance use in adolescents require unique considerations, including the following:

  • Social factors, particularly strong peer influences, have a significant impact on adolescent substance use [1,2].
  • Experimentation with substances, especially with alcohol, is common among adolescents and is often considered normative behavior [3].
  • HIV-infected adolescents presenting for treatment typically demonstrate a high degree of co-occurring mental health symptoms or prior mental health diagnoses [4], which frequently precede the onset of problem substance use.

Marijuana and alcohol are used frequently by HIV-infected adolescents. Use of heroin, methamphetamine, and cocaine is less commonly reported [5,6]; however, males and those with asymptomatic HIV infection may be more likely to use these substances [5,7]. In the general adolescent population, the misuse of prescription opioids is increasing [8]. Methamphetamine use is increasing among young adults (aged 18 to 26), particularly among men who have sex with men [9]. Awareness of factors that influence the use of other types of substances among adolescents is also important. Adolescents in school may be at risk for misusing stimulants, such as methylphenidate, for enhancing academic performance [10]. Adolescents involved in sports or concerned with body image may be at risk for using anabolic steroids to enhance their athletic performance and appearance [11].

This guideline provides guidance on how to:

  • Identify HIV-infected adolescents at risk for substance use
  • Communicate with adolescents about substance use
  • Screen and assess for substance use in HIV-infected adolescents
  • Implement appropriate substance use interventions and make necessary referrals
References:
  1. Kendler KS, Schmitt E, Aggen SH, et al. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry 2008;65:674-682. [PubMed]
  2. Simons-Morton B. Social influences on adolescent substance use. Am J Health Behav 2007;31:672-684. [PubMed]
  3. National Institute on Drug Abuse. Monitoring the Future: National Survey Results on Drug Use, 1975-2007. Bethesda, MD: National Institute on Drug Abuse, US Department of Health and Human Services; 2008. Available at: www.monitoringthefuture.org/pubs.htm
  4. Pao M, Lyon M, D’Angelo LJ, et al. Psychiatric diagnoses in adolescents seropositive for the human immunodeficiency virus. Arch Pediatr Adolesc Med 2000;154:240-244. [PubMed]
  5. Wilson CM, Houser J, Partlow C, et al. The REACH (Reaching for excellence in adolescent care and health) Project: Study design, methods, and population profile. J Adolesc Health 2001;29S:8-18. [PubMed]
  6. Lightfoot M, Swendeman D, Rotheram-Borus MJ, et al. Risk behaviors of youth living with HIV: Pre- and post-HAART. Am J Health Behav2005;29:162-171. [PubMed]
  7. Rotheram-Borus MJ, Lee M, Zhou S, et al. Variation in health and risk behavior among youth living with HIV. AIDS Educ Prev 2001;13:42-54. [PubMed]
  8. Levine DA. “Pharming”: The abuse of prescription and over-the-counter drugs in teens. Curr Opin Pediatr 2007;19:270-274. [PubMed]
  9. Iritani BJ, Hallfors DD, Bauer DJ. Crystal methamphetamine use among young adults in the USA. Addiction 2007;102:1102-1113. [PubMed]
  10. Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008;47:21-31. [PubMed]
  11. Castillo EM, Comstock RD. Prevalence of use of performance-enhancing substances among United States adolescents. Pediatr Clin North Am2007;54:663-675. [PubMed]

Risk Factors

February 2009

RECOMMENDATION
  • Clinicians should be able to recognize adolescents who are at high risk for substance use.

The developmental changes that occur during adolescence, coupled with HIV infection, can increase the use of alcohol and other substances. These patients may feel a sense of vulnerability, which may further place them at risk for substance use. Understanding adolescent development is critical to helping adolescents mature into well-adjusted adults. 

Assessment of the emotional support available to HIV-infected adolescents is essential, including whether an adult role model is present. Homeless and transient adolescents, as well as adolescents in foster care, are particularly vulnerable to social isolation and often require intensive case management. Because support networks may include family, friends, sexual partners, healthcare providers, teachers, counselors, clergy, and adult role models, clinicians should be inclusive when inquiring about who is significant in adolescents’ lives.

Many of the individual, family, and social factors associated with increased risk for substance use in adolescents are prevalent in HIV-infected adolescents. Clinicians can use this information to help identify HIV-infected adolescents who may be at particular risk for substance use.

Potential Risk Factors for Substance Use

Mental health diagnoses: Adolescents with diagnoses of depression, anxiety, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and conduct disorder are more likely to use substances than adolescents with no mental health diagnosis [1-3].

Sexual, emotional and physical abuse: Abuse and neglect in childhood is consistently associated with a high likelihood of substance use during adolescence in both males and females [4-6]. Violence associated with dating is also linked to high levels of alcohol and marijuana use in adolescents [7]. One study found that one in seven young men who have sex with men (YMSM) experienced childhood sexual abuse and that adolescents with a history of being sexually abused by adults were more likely to use substances than their peers [8].

Homelessness or street involvement: Early experiences of homelessness may predict substance use in adolescents and young adults [9]. Homelessness is associated with the use of a variety of substances, including alcohol, methamphetamine, and injection drug use [5]. Two studies of YMSM found that homelessness and running away from home were associated with substance use [10,11].

Lesbian, gay, bisexual, and transgendered (LGBT): LGBT adolescents, especially lesbian and bisexual adolescents, have higher rates of substance use than heterosexual adolescents, but little information on the moderating or mediating factors is available [12]. LGBT adolescents with other risk factors for substance use, including homelessness, residential instability, mental health diagnoses, peer substance use, and childhood abuse, have high rates of substance use [8,10,11,13,14]. Among YMSM, HIV-infected individuals may be more likely to use substances, especially methamphetamine, compared to their non-infected peers [15]. Transgender adolescents are at risk for illicit hormone use.

HIV-infected parents and family functioning: Family functioning plays a major role in predicting substance use in children of HIV-infected parents [16]. In one large study, family functioning was disrupted frequently by substance use. Over one-half of children of HIV-infected parents were not in the parents’ custody; the most common reason for non-parental custody was parental substance use [17]. Children of HIV-infected parents have high rates of mental health diagnoses, placing them at additional risk for substance use [18].

Parental substance use: Parental substance use predicts early and increased levels of alcohol and substance use in children and adolescents [19-21]. Protective factors for adolescent substance use in families with parental substance use include close sibling relationships and parental disapproval of children’s substance use [21,22].

Incarceration: Adolescent incarceration is associated with increased substance use [1,2].

Foster care: Evidence in this area is limited due to restrictions on research involving adolescents in the foster care system. However, available research shows that adolescents in foster care have higher rates of substance use than adolescents not in foster care [23]. Substance use among those in foster care is especially common in adolescents who have mental health diagnoses [24,25].

Early puberty: Early puberty is associated with both increased substance use and adolescent pregnancy [26].

Adolescent pregnancy: Adolescent mothers use substances more often than their peers, and this difference persists into young adulthood [27].

Peers who use substances: Peer influence is important in predicting substance use in adolescents, and adolescents who use substances are likely to have friends who also use substances [28,29].

Educational experience: Lack of educational attainment or school attendance is a marker for substance use in adolescents [30]. Inversely, some adolescents may experience pressure to increase their academic performance, which can place them at risk for using cognitive-enhancing substances, such as methylphenidate [31].

Body image and athletics: Some adolescents may experience pressure to alter their appearance through body-building or increase their athletic performance, both of which can place them at risk for using performance-enhancing substances, such as steroids [32].

Tobacco use: Tobacco use has been consistently reported in adolescents receiving treatment for alcohol and substance dependence [33,34], and adolescent smoking has been suggested as an indicator for both alcohol use and dependence [35,36].

References:
  1. Tolou-Shams M, Brown LK, Houck C, et al.; Project SHIELD Study Group. The association between depressive symptoms, substance use, and HIV risk among youth with an arrest history. J Stud Alcohol Drugs 2008;69:58-64. [PubMed]
  2. Tolou-Shams M, Brown LK, Gordon G, et al; Project SHIELD Study Group. Arrest history as an indicator of adolescent/young adult substance use and HIV risk. Drug Alcohol Depend 2007;88:87-90. [PubMed]
  3. Elkins IJ, McGue M, Iacono WG. Prospective effects of attention-deficit/hyperactivity disorder, conduct disorder, and sex on adolescent substance use. Arch Gen Psychiatry 2007;64:1145-1152. [PubMed]
  4. Dunlap E, Golub A, Johnson BD. Girls’ sexual development in the inner city: From compelled childhood sexual contact to sex-for-things exchanges.J Child Sex Abus 2003;12:73-96. [PubMed]
  5. Coady MH, Latka MH, Thiede H, et al. Housing status and associated differences in HIV risk behaviors among young injection drug users (IDUs).AIDS Behav 2007;11:854-863. [PubMed]
  6. Arata CM, Langhinrichsen-Rohling J, Bowers D, et al. Differential correlates of multi-type maltreatment among urban youth. Child Abuse Negl 2007;31:393-415. [PubMed]
  7. Eaton DK, Davis KS, Barrios L, et al. Associations of dating violence victimization with lifetime participation, co-occurrence, and early initiation of risk behaviors among U.S. high school students. J Interpers Violence 2007;22:585-602. [PubMed]
  8. Brennan DJ, Hellerstedt WL, Ross MW, et al. History of childhood sexual abuse and HIV risk behaviors in homosexual and bisexual men. Am J Public Health 2007;97:1107-1112. [PubMed]
  9. Johnson TP, Fendrich M. Homelessness and drug use: Evidence from a community sample. Am J Prev Med 2007;32(6 Suppl):S211-S218. [PubMed]
  10. LaLota M, Kwan BW, Waters M, et al. The Miami, Florida, Young Men’s Survey: HIV prevalence and risk behaviors among urban young men who have sex with men who have ever runaway. J Urban Health 2005;82:327-338. [PubMed]
  11. Kipke MD, Weiss G, Wong CF. Residential status as a risk factor for drug use and HIV risk among young men who have sex with men. AIDS Behav2007;11(6 Suppl):56-69. [PubMed]
  12. Marshal MP, Friedman MS, Stall R, et al. Sexual orientation and adolescent substance use: A meta-analysis and methodological review. Addiction2008;103:546-556. [PubMed]
  13. Rosario M, Schrimshaw EW, Hunter J. Predictors of substance use over time among gay, lesbian, and bisexual youths: An examination of three hypotheses. Addict Behav 2004;29:1623-1631. [PubMed]
  14. Cochran BN, Stewart AJ, Ginzler JA, et al. Challenges faced by homeless sexual minorities: Comparison of gay, lesbian, bisexual, and transgender homeless adolescents with their heterosexual counterparts. Am J Public Health 2002;92:773-777. [PubMed]
  15. Garafalo R, Mustanski BS, McKirnan DJ, et al. Methamphetamine and young men who have sex with men: Understanding patterns and correlates of use and the association with HIV-related sexual risk. Arch Pediatr Adolesc Med 2007;161:591-596. [PubMed]
  16. Rosenblum A, Magura S, Fong C, et al. Substance use among young adolescents in HIV-affected families: Resiliency, peer deviance, and family functioning. Subst Use Misuse 2005;40:581-603. [PubMed]
  17. Cowgill BO, Beckett MK, Corona R, et al. Children of HIV-infected parents: Custody status in a nationally representative sample. Pediatrics2007;120:494-503. [PubMed]
  18. Pilowsky DJ, Zybert PA, Hsieh PW, et al. Children of HIV-positive drug-using parents. J Am Acad Child Adolesc Psychiatry 2003;42:950-956. [PubMed]
  19. 30. Walden B, Iacono WG, McGue M. Trajectories of change in adolescent substance use and symptomatology: Impact of paternal and maternal substance use disorders. Psychol Addict Behav 2007;21:35-43. [PubMed]
  20. Ohanessian CM, Hesselbrock VM. Paternal alcoholism and youth substance use: The indirect effects of negative affect, conduct problems, and risk taking. J Adolesc Health 2008;42:198-200. [PubMed]
  21. Ohanessian CM, Hesselbrock VM. Do personality characteristics and risk taking mediate the relationship between paternal substance dependence and adolescent substance use? Addict Behav 2007;32:1852-1862. [PubMed]
  22. Lam WK, Cance JD, Eke AN, et al. Children of African-American mothers who use crack cocaine: Parenting influences on youth substance use. J Pediatr Psychol 2007;32:877-887. [PubMed]
  23. White CR, O’Brien K, White J, et al. Alcohol and drug use among alumni of foster care: Decreasing dependency through improvement of foster care experiences. J Behav Health Serv Res 2008;35:419-434. [PubMed]
  24. Pilowsky DJ, Wu LT. Psychiatric symptoms and substance use disorders in a nationally representative sample of American adolescents involved with foster care. J Adolesc Health 2006;38:351-358. [PubMed]
  25. Vaughn MG, Ollie MT, McMillen JC, et al. Substance use and abuse among older youth in foster care. Addict Behav 2007;32:1929-1635. [PubMed]
  26. Deardorff J, Gonzales NA, Christopher FS, et al. Early puberty and adolescent pregnancy: The influence of alcohol use. Pediatrics 2005;116:1451-1456. [PubMed]
  27. Gillmore MR, Gilchrist L, Lee J, et al. Women who gave birth as unmarried adolescents: Trends in substance use from adolescence to adulthood. J Adolesc Health 2006;39:237-243. [PubMed]
  28. Simons-Morton B. Social influences on adolescent substance use. Am J Health Behav 2007;31:672-684. [PubMed]
  29. Mason WA, Hitchings JE, McMahon RJ, et al. A test of three alternative hypotheses regarding the effects of early delinquency on adolescent psychosocial functioning and substance involvement. J Abnorm Child Psychol 2007;35:831-843. [PubMed]
  30. King KM, Meehan BT, Trim RS, et al. Marker or mediator? The effects of adolescent substance use on young adult educational attainment. Addiction2006;101:1730-1740. [PubMed]
  31. Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008;47:21-31. [PubMed]
  32. Castillo EM, Comstock RD. Prevalence of use of performance-enhancing substances among United States adolescents. Pediatr Clin North Am2007;54:663-675. [PubMed]
  33. Myers MG, Kelly JF. Cigarette smoking among adolescents with alcohol and other drug use problems. Alcohol Res Health 2006;29:221-227. [PubMed]
  34. Myers MG, Doran NM, Brown SA. Is cigarette smoking related to alcohol use during the 8 years following treatment for adolescent alcohol and other drug abuse? Alcohol Alcohol 2007;42:226-233. [PubMed]
  35. Orlando M, Tucker JS, Ellickson PL, et al. Concurrent use of alcohol and cigarettes from adolescence to young adulthood: An examination of developmental trajectories and outcomes. Subst Use Misuse 2005;40:1051-1069. [PubMed]
  36. Mathers M, Toumbourou JW, Catalano RF. Consequences of youth tobacco use: A review of prospective behavioural studies.Addiction 2006;101:948-958. [PubMed]

Communication About Substance Use

February 2009

RECOMMENDATIONS
  • Clinicians should convey a nonjudgmental attitude toward adolescents when discussing substance use and should use words and concepts appropriate to the patient’s cultural background and cognitive, linguistic, and emotional development.
  • Clinicians should reassure adolescent patients that discussions regarding substance use are confidential.

Trust between the patient and clinician is essential for an honest discussion that differentiates among experimentation, use, and abuse. To establish rapport and facilitate engagement, clinicians need to have a nonjudgmental attitude and use words and concepts appropriate to the patient’s cultural background and cognitive, linguistic, and emotional development. Effective communication with adolescents about substance use includes the following:

  • Assurances of confidentiality. Adolescent patients are often concerned about confidentiality and about the consequences of providing honest answers to questions about substance use.
  • Rationale for screening. An explanation of why the screening questions are important. This can help establish trust and enable clinicians to educate patients about the effects of substance use on the course of their HIV illness.
  • Common terminology. Asking the patient what terms he/she uses, such as, “What do you call heroin? Do you have a name for being on ecstasy?” can teach the healthcare provider what the adolescent knows about the drug scene and can help the clinician obtain information about the patient’s experiences with and understanding about substance use. However, providers should avoid using slang terms unless they are very adept at working with this population; otherwise, this can seem patronizing, particularly because adolescents have been shown to understand conventional medical terminology.
KEY POINT
Patients who are not ready to discuss substance use may develop trust in a clinician who demonstrates competence in addressing other challenges, such as housing instability or other case management needs. Once such trust is established, the patient may become comfortable with discussing substance use.

History and Screening

February 2009

RECOMMENDATIONS
  • Clinicians should obtain a comprehensive history from adolescent patients that includes substance use and mental health screening and psychosocial assessment. Screening should include all levels of alcohol and substance use.
  • Clinicians should screen HIV-infected adolescents for substance use at baseline and every 3 months thereafter. If the HIV-infected adolescent’s initial drug screening result is positive, or if the patient has a history of substance use, the clinician should re-evaluate the patient’s drug use more frequently as needed.
  • As part of the history-taking process, clinicians should incorporate selected brief screening instruments and discuss the confidentiality of screening with HIV-infected adolescents. The chosen screening instruments should be individually tailored for optimal use at baseline and follow-up visits and adjusted for the patient’s substance use history.

A comprehensive history is essential for identifying substance use, guiding management of patients with psychosocial stressors, and accurately establishing mental health diagnoses in HIV-infected adolescents. A nonjudgmental and caring approach to history-taking may elicit more accurate responses regarding sensitive issues, including substance use.

KEY POINT
Screening for all levels of alcohol and other substance use in HIV-infected adolescents is important because:

  • Both alcohol and substance use are risk factors for HIV transmission and STI acquisition
  • Even intermittent use can interfere with adherence to medications [1], raise the risk of drug-drug interactions, and reduce the patient’s ability to practice safer sex

Substance use screening tools can be integrated easily into the primary care of adolescents. Some programs have their own screening tools with questions tailored to their clinic setting. A patient’s answers to the questions listed below can provide useful information about his/her attitudes about and frequency of substance use and can help clinicians determine whether further substance use assessment is necessary.

Questions to Assess Attitudes About and Frequency of Substance Use*

Ask about current and past substance use in a nonjudgmental way

  • Do you drink alcohol?
  • Have you experimented with or used other drugs?

Ask about specific substances (e.g., marijuana, alcohol, stimulants, opiates, and sedatives). Questions that target specific substances can elicit more accurate responses. For example:

  • Did you smoke marijuana today, yesterday, recently?
  • How many times do you smoke during the week?
  • What do you like about it?
  • What do you dislike about it?

It is also important to include a question that specifically addresses over-the-counter and prescription medications, such as cough syrup (i.e., dextromethorphan), ephedrine, cognitive stimulants (e.g., methylphenidate and other “study drugs”), anabolic steroids, prescription opiates, and benzodiazepines, as well as family members’ prescriptions that he/she may be able to access.

Patients who use multiple drugs may succeed at discontinuing the use of one drug while continuing to use others. Clinicians should phrase questions to inquire into the use of other substances as well.

*For information about specific substances, refer to What Are These Drugs?

Some clinicians may prefer validated tools. The SAMHSA Center for Substance Abuse Treatment (CSAT) TIP 31 guidelines Screening and Assessing Adolescents for Substance Use Disorders provide a list of recommended tools that are appropriate for adolescent substance use screening. Although screening tools with greater numbers of items have also been validated, brief screening instruments are preferable in the clinic setting because large-item screening tools may not be practical when time is limited. Additional information about substance use screening is also available in Screening and Ongoing Assessment for Substance Use as well as the Substance Use Screening Quick Reference Guide.

The selected tool should be tailored for optimal use at initial and follow-up visits and adjusted according to the patient’s substance use history.

KEY POINTS
  • Ongoing assessment is important. However, adolescent patients who express a lack of readiness to address the issue of substance use may not provide honest answers and may become alienated if they feel ongoing pressure to continually discuss the topic.
  • Signs of social withdrawal or a sudden change in behavior or peer influences may be an indicator of substance use and require further assessment.

Unless there is a life-threatening medical emergency, drug testing should only be conducted with the knowledge and consent of the adolescent. The patient should be told that it is a part of the treatment plan and may provide useful information to the provider as well as a means for the patient to avoid use. However, laboratory tests yield a narrow range of information; severity of use and the consequences of that use cannot be obtained from testing for the presence of drugs in urine and blood [2]. Drug monitoring cannot substitute for an ongoing therapeutic alliance with the adolescent.

References:
  1. Pao M, Lyon M, D’Angelo LJ, et al. Psychiatric diagnoses in adolescents seropositive for the human immunodeficiency virus. Arch Pediatr Adolesc Med 2000;154:240-244. [PubMed]
  2. Casavant MJ. Urine drug screening in adolescents. Pediatr Clin North Am 2002;49:317-327. [PubMed]

Intervention Strategies

February 2009

For HIV-infected adolescents, substance use is often just one problem among many psychosocial problems that need to be addressed [1]. For some adolescents, substance use may be a transient reaction to learning that they are HIV-infected or may be a result of parental substance use. Substance use may also be a result of an untreated or undertreated mental health diagnosis (see Mental Health Disorders, HIV Infection, and Substance-Use). Information about mental health screening and treatment is available in the Mental Health Guidelines.

Determination of the most appropriate intervention for an individual recognizes the context of the HIV-infected adolescent’s chronicity of use and degree of dependence. The American Society of Addiction Medicine criteria can help clinicians determine which patients have serious problems that require a higher level of substance use intervention [2]. Substance use treatment and related services are also available (see Resources for Adolescent Substance Use Treatment).

The strategies outlined below have been used primarily as interventions for alcohol, marijuana, and opioid use in adolescents. Unfortunately, the efficacy of such interventions for addressing adolescent methamphetamine use has not been determined. Because methamphetamine dependence often requires psychotherapeutic intervention, methamphetamine programs for adolescents are needed. Cognitive-behavioral approaches that have demonstrated promising results in adults, such as the Matrix Model [3], have not yet been adapted for adolescents, and pharmacotherapy for methamphetamine has not been established for either adults or adolescents. At the present time, standard youth intervention programs, such as those discussed below, are likely to be more appropriate for adolescents than methamphetamine programs for older adults.

Harm-Reduction Approach

RECOMMENDATION
  • Clinicians should use harm-reduction principles for adolescents who are not ready, or not willing, to make abstinence a goal. Such harm-reduction strategies include counseling adolescents to reduce harmful use, such as binge drinking, heavy or daily marijuana use, and polydrug use, as well as referring injection drug-using adolescents and young adults to syringe exchange programs.

The American Academy of Child and Adolescent Psychiatry (1997) defines harm reduction as a decrease in the use and adverse effects of substances, a reduction in the severity and frequency of relapses, and improvement in one or more areas of the adolescent’s functioning, including academic achievement or family functioning. Harm reduction is intended to engage the patient in health care through the clinician’s nonjudgmental stance toward the patient’s current substance use. Adolescents who are not ready or who are unwilling to abstain from alcohol or other substances may be receptive to education and encouragement from a clinician who focuses on reducing harmful use instead of insisting on abstinence. Such education can include:

  • Caution against binge drinking, heavy or daily marijuana use, and polydrug use, with a focus on educating patients about the risk of drug-drug interactions, both between substances and between substances and HIV medications, and the health effects of heavy substance use
  • Encouragement of behaviors that reduce HIV transmission risk, such as not sharing equipment used for administering substances, including straws for snorting and equipment for injecting substances, and referral to syringe access exchange programs as available

Harm reduction is developmentally appropriate for adolescents who consider some level of substance use normative in their peer group, because the approach emphasizes safety if the patient is using, rather than lifetime abstinence [4].

Refer to Working With the Active User for more information regarding harm-reduction strategies.

Brief Interventions

RECOMMENDATION
  • Clinicians should implement brief interventions for HIV-infected adolescents when a problem with substance use is identified.

Brief interventions are short-term, less intensive alternatives to traditional substance use treatment modalities. These interventions share a common goal of enhancing a person’s motivation and ability to change. Information about risks of substance use, means to reduce problems related to use, benefits to reducing use, and referrals to more extensive services are usually included in brief interventions. Because brief interventions have been shown to be effective in reducing substance use and substance-related harms in adolescents, including use of alcohol [5], marijuana [6,7], and other drugs [8,9], clinicians should implement brief interventions when a problem with substance use is identified.

Time limitations and limited provider training have been identified as barriers to effective use of brief interventions [10]. It has been suggested that all healthcare providers, including nurses, may effectively implement brief interventions.

Preliminary research indicates brief interventions may not be as effective for reducing cigarette smoking as for reducing alcohol, marijuana, and other substance use [6]. Mixed results with some populations at high risk for problem substance use, including homeless adolescents, indicate that there is a need for further research and alternative interventions for reduction of substance use and its harms during adolescence.

Refer to Working With the Active User for more information regarding brief interventions.

Motivational interviewing: Motivational interviewing is a brief psychotherapeutic intervention to increase the likelihood of a patient’s consideration, initiation, and maintenance of specific change strategies to reduce harmful behavior. Motivational interviewing is one type of brief intervention shown to be effective with adolescents [7]. The four components of motivational interviewing are described below:

  • Expressing empathy: Understanding and being aware of and sensitive to the feelings, thoughts, and experiences of another. Accomplished through reflective listening.
  • Supporting self-efficacy: Supporting the patient with the sense that an individual can identify and meet one’s needs and goals.
  • Avoiding argumentation and rolling with resistance: Listening to the patient’s resistance to change. Working collaboratively with the patient to develop his/her input regarding the treatment plan.
  • Discovering discrepancies: Helping patients identify discrepancies between their current behavior and desired future behavior.

More information on motivational interviewing, training, and a video on motivational interviewing for adolescents who use marijuana are available at the Motivational Interviewing website

Motivational Enhancement Therapy: Motivational enhancement therapy is a brief intervention that combines motivational interviewing with cognitive-behavioral techniques, such as problem-solving. A four-session motivational enhancement therapy intervention for HIV-infected adolescents and young adults aged 16 to 25 was shown to be effective in reducing alcohol use. It was also associated with improved health outcomes, such as a reduction in HIV viral load [11,12].

Group Interventions

Adolescents may prefer group treatment over other options for substance use treatment. Group interventions using a cognitive-behavioral approach have been shown to be effective in lowering rates of substance use among HIV-infected adolescent participants [13]. These cognitive-behavioral strategies emphasize how contextual and environmental factors can influence adolescents’ response to stressful situations, including problem-solving and social-negotiating strategies. Group interventions for substance use have been developed for HIV-infected adolescents and provide risk education and social-negotiating and problem-solving training (see the CDC’s Diffusion of Effective Behavioral Intervention).

In most studies, group interventions were not associated with negative outcomes [14,15]. Group interventions may be challenging to implement in some areas, due to scheduling and confidentiality concerns. Telephone and internet-based groups have been suggested as alternatives to the traditional group format [16].

Pharmacotherapy

With the exception of opioid agonist therapy and smoking cessation, the efficacy of pharmacotherapy for substance use has not been well established in adolescents.

RECOMMENDATION
  • Clinicians should refer injection drug-using adolescents for opioid-dependence treatment or more intensive levels of care as appropriate, such as extended counseling and case management.

Pharmacotherapy for opioid dependence: Among adults, methadone maintenance has been shown to be highly efficacious in reducing heroin use, reducing HIV risk behaviors, and supporting ARV treatment adherence [17,18]. A review of existing studies of adolescents found that methadone had the highest retention rate over other modalities and may be more effective in reducing illicit drug use [19]. However, many methadone maintenance programs lack resources for addressing co-occurring psychosocial and mental health concerns in adolescents. For patients who stay in treatment for at least 6 months, other modalities, including therapeutic communities and abstinence-based treatment with and without naltrexone, have the best long-term outcomes, with greater reductions in the use of opiates and other substances, as well as increased rates of employment [19]. Although therapeutic communities and abstinence- based treatment may have greater success in helping patients with long-term adjustment, these programs have a lower initial retention rate in comparison with methadone maintenance.

Many opioid dependence treatment facilities, including methadone maintenance programs, do not accept individuals who are younger than 18 years of age. For facilities that do treat individuals younger than 18, Federal law requires two documented failures of drug-free detoxification and verification of 2 years of opioid dependence before admission.

Buprenorphine prescribed by an ambulatory care clinician may be a suitable alternative to illicit opioid use for many adolescents. Buprenorphine may also be used both for maintenance and for detoxification and appears to have similar benefits to methadone with several advantages, including: (1) it can be prescribed by any physician who has taken an 8-hour course, rather than only in specialized clinics; (2) as a partial agonist, it has a higher safety profile; and (3) the formulation Suboxone includes naloxone to reduce the misuse of buprenorphine. For more information regarding treatment with buprenorphine, refer to the Substance Use guidelines appendix, Use of Buprenorphine in HIV-Infected Patients.

Pharmacotherapy for smoking cessation: Cessation of smoking among adolescents may reduce their risk for future substance dependence, particularly alcohol dependence [20]. For information regarding pharmacotherapy for smoking cessation, see Smoking Cessation in HIV-Infected Patients.

References:
  1. Jessor, R. Risk behavior in adolescence: A psychosocial framework for understanding and action. J Adolesc Health 1991;12:597-605. [PubMed]
  2. American Society of Addiction Medicine. Available at: www.asam.org/PatientPlacementCriteria.html
  3. Shoptaw S, Rawson RA, McCann MJ, et al. The Matrix model of outpatient stimulant abuse treatment: Evidence of efficacy. J Addict Dis 1994;13:129-141. [PubMed]
  4. Masterman PW, Kelly AB. Reaching adolescents who drink harmfully: Fitting intervention to developmental reality. J Substance Abuse Treatment2003;24:347-355. [PubMed]
  5. Gray E, McCambridge J, Strang J. The effectiveness of motivational interviewing delivered by youth workers in reducing drinking, cigarette and cannabis smoking among young people: Quasi-experimental pilot study. Alcohol Alcohol 2005;40:535-539. [PubMed]
  6. McCambridge J, Strang J. The efficacy of single-session motivational interviewing in reducing drug consumption and perceptions of drug-related risk and harm among young people: Results from a multi-site cluster randomized trial. Addiction 2004;99:39-52. [PubMed]
  7. Martin G, Copeland J. The adolescent cannabis check-up: Randomized trial of a brief intervention for young cannabis users. J Subst Abuse Treat2008;34:407-414. [PubMed]
  8. Tait RJ, Hulse GK. A systematic review of the effectiveness of brief interventions with substance using adolescents by type of drug. Drug Alcohol Rev 2003;22:337-346. [PubMed]
  9. Tevyaw TO, Monti PM. Motivational enhancement and other brief interventions for adolescent substance abuse: Foundations, applications and evaluations. Addiction 2004;99(Suppl 2):63-75. [PubMed]
  10. Roche AM, Freeman T. Brief interventions: Good in theory but weak in practice. Drug Alcohol Rev 2004;23:11-18. [PubMed]
  11. Naar-King S, Wright K, Parsons JT, et al. Healthy Choices: Motivational enhancement therapy for health risk behaviors in HIV-positive youth. AIDS Educ Prev 2006;18:1-11. [PubMed]
  12. Naar-King S, Lam P, Wang B, et al. Brief report: Maintenance of effects of motivational enhancement therapy to improve risk behaviors and HIV-related health in a randomized controlled trial of youth living with HIV. J Pediatr Psychol 2008;33:441-445. [PubMed]
  13. Rotheram-Borus MJ, Lee MB, Murphy DA, et al. Efficacy of a preventive intervention for youths living with HIV. Am J Public Health 2001;91:400-405. [PubMed]
  14. Kaminer Y. Challenges and opportunities of group therapy for adolescent substance abuse: A critical review. Addict Behav 2005;30:1765-1774. [PubMed]
  15. French MT, Zavala SK, McCollister KE, et al. Cost-effectiveness of four interventions for adolescents with a substance use disorder. J Subst Abuse Treat 2008;34:272-281. [PubMed]
  16. Lightfoot M, Rotheram-Borus MJ, Tevendale H. An HIV-preventive intervention for youth living with HIV. Behav Modif 2007;31:345-363. [PubMed]
  17. Joseph H, Stancliff S, Langrod J. Methadone maintenance treatment (MMT): A review of historical and clinical issues. Mt Sinai J Med 2000;67:347-364. [PubMed]
  18. Altice FL, Sullivan LE, Smith-Rohrberg D, et al. The potential role of buprenorphine in the treatment of opioid dependence in HIV-infected individuals and in HIV infection prevention. Clin Infect Dis 2006;43(Suppl 4):S178-S183. [PubMed]
  19. Hopfer CJ, Khuri E, Crowley TJ, et al. Adolescent heroin use: A review of the descriptive and treatment literature. J Subst Abuse Treat 2002;23:231-237. [PubMed]
  20. Orlando M, Tucker JS, Ellickson PL, et al. Concurrent use of alcohol and cigarettes from adolescence to young adulthood: An examination of developmental trajectories and outcomes. Subst Use Misuse 2005;40:1051-1069. [PubMed]

Mental Health Treatment

February 2009

RECOMMENDATION
  • HIV-infected adolescents with co-occurring substance use and mental health diagnoses should be carefully assessed for psychotropic management of their mental health diagnosis.

Effective psychotropic management of co-occurring mental health diagnoses can often aid in reducing substance use, including alcohol and marijuana. Adolescents with comorbid mental health diagnoses, especially depression and bipolar disorder, generally decrease their use of substances, including alcohol and marijuana, when they received psychotropic management for their mental health diagnosis [1]. Accordingly, adolescents with co-occurring mental health diagnoses should be assessed for psychotropic management.

For additional information regarding mental health considerations for substance users, refer to Mental Health Disorders, HIV Infection, and Substance Use.

Reference:
  1. Waxmonsky JG, Wilens TE. Pharmacotherapy of adolescent substance use disorders: A review of the literature. J Child Adolesc Psychcopharmacol2005;15:810-825. [PubMed]

Referrals for Substance Use Treatment

February 2009

RECOMMENDATIONS
  • Clinicians should have access to experienced case managers who can address the multiple disciplines involved in working with HIV-infected substance-using adolescents.
  • Clinicians should recognize that many adolescents do not know about substance use intervention services or how to access them.
  • With the patient’s consent, substance use programs should make every effort to involve the adolescent’s family and supportive adults in their care when appropriate.
  • Substance use programs and HIV care providers should collaborate in the development of treatment plans for adolescents who are engaged in both types of care.

Adolescents often do not know where they can obtain mental health and substance use services in their community and are seldom motivated to self-refer to substance use treatment. Typically, they are referred by a parent, clinician, juvenile justice, school, child welfare, or other government/community agency.

Linking HIV-infected adolescents to appropriate adolescent-specific drug treatment is difficult because few programs specialize in the needs of adolescents, and adult programs that do accept young adults 18 years of age and older may not be sensitive to the numerous other needs of an HIV-infected adolescent. Barriers to care include lack of financial resources and/or insurance and mistrust of healthcare professionals. Some HIV-infected adolescents who are addicted to substances may not require rehabilitative strategies as much as they require strategies that enable them to develop life skills.

The SAMHSA Center for Substance Abuse Treatment (CSAT) TIP 32 guidelines, Treatment of Adolescents with Substance Use Disorders [1], emphasize the differences between treating adults and adolescents and discuss treatment options that emphasize adolescents’ special needs, including attention to their cognitive, emotional, and social development. CSAT has also published a comprehensive description of the continuum of adolescent treatment options based on multiple client assessment criteria [1]. Familiarity with the following treatment levels can enable clinicians to individualize the appropriate level of treatment for each patient:

  • Outpatient
  • Intensive outpatient options
  • Long-term residential psychosocial care (therapeutic communities)
  • Half-way houses
  • Group home living arrangements for adolescents who have experienced significant drug abuse

Some adolescents, especially those in the earlier stages of dependence who have supportive families and less severe coexisting problems, respond better in outpatient environments, where they can maintain their academic and family lives. Hospitalization may be indicated in some cases (see below).

A list of community resources should be easily accessible to HIV-infected adolescents visiting the clinic setting. One resource for locating substance use treatment programs for adolescents is the SAMHSA Substance Abuse Treatment Facility Locator.

Indicators for hospitalization of HIV-infected substance-using adolescents:

  • Overdose that cannot be safely treated in the outpatient or emergency room setting (e.g., severe respiratory depression, coma)
  • Risk for a severe or complicated withdrawal syndrome, including dependence on multiple drugs, history of delirium tremens
  • Acute or chronic medical conditions that make detoxification in a residential or ambulatory setting unsafe
  • A documented history of not engaging in, or benefiting from, treatment in a less intensive setting
  • Marked psychiatric comorbidity with an acute danger to self or others
  • No response to less intensive treatment efforts
  • Substance use poses an ongoing threat to own physical and mental health
Reference:
  1. McLellan T, Dembo R. Screening and Assessment of Alcohol- and Other Drug-Abusing Adolescents. Rockville, MD: US Dept of Health and Human Services; 1993. Treatment improvement protocol (TIP) series. Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. DHHS Publication No. (SMA) 93-2009. Available at: http://store.samhsa.gov/list/series?name=TIP-Series-Treatment-Improvement-Protocols-TIPS-

Maintaining Care

February 2009

RECOMMENDATIONS
  • Clinicians should ensure that HIV-infected adolescents are engaged in medical care regardless of whether or not they are actively using drugs.
  • Clinicians should include substance-using HIV-infected adolescents in the medical treatment planning process as early as possible.

Patients with comorbid substance use and HIV infection are more likely to leave medical treatment when they are given treatment goals that they are not ready to accept. The inclusion of patients early in the planning process of medical treatment may lead to more successful outcomes. Medical treatment goals will vary according to the adolescent’s needs, which will depend on his/her level of family support and pattern of use of alcohol and other substances. However, if a patient does not fully understand his/her HIV diagnosis and management, he/she may not be able to achieve the desired clinical outcome. In such cases, clinicians may need to address the patient’s substance use before engaging him/her in medical care.

For additional information about maintaining substance-using patients in care, refer to Working With the Active User.

Relapse Prevention

February 2009

RECOMMENDATIONS
  • Clinicians should coordinate with relapse prevention programs and mental health care providers when caring for HIV-infected adolescents with a history of substance or alcohol dependence.
  • Clinicians should ask HIV-infected adolescents in early recovery at each visit about the date of last use of substances, alcohol, and tobacco.

By definition, recovery from substance use behavior can be interrupted by periods of relapse. Relapse is defined by the American Society of Addiction Medicine as the “recurrence of psychoactive substance-dependent behavior in an individual who has previously achieved and maintained abstinence for a significant period of time beyond withdrawal” [1].

Patients with a known history of substance/alcohol dependence are at high risk for relapse, particularly when stressed by a new diagnosis of HIV or its complications. Clinicians should collaborate with relapse prevention programs and mental health providers as part of the overall care of patients with a history of substance or alcohol dependence. Relapse in patients who are in early recovery can be better identified when patients are asked at each visit about the date of last use of substances, alcohol, and tobacco.

Relapse is not a failure but an opportunity to learn from what happened and to change tactics to more effectively prevent future relapse.

When a patient relapses, the clinician should:

  • Be nonjudgmental and voice continued optimism
  • Ask what the specific circumstances were that led to the relapse
  • Encourage a return to treatment
  • Discuss difficulties and stresses
  • Reassess the need to initiate pharmacotherapy or adjust doses
  • Refer to or include other providers, such as social workers, in the patient’s care
  • Schedule more frequent visits

For additional information regarding relapse prevention, refer to Working With the Active User.

Reference:
  1. American Society of Addiction Medicine. Available at: www.asam.org/PatientPlacementCriteria.html

All Recommendations

Subcommittee on the Care of Adolescents with HIV Infection, February 2009

ALL RECOMMENDATIONS: SUBSTANCE USE AMONG ADOLESCENTS AND YOUNG ADULTS WITH HIV INFECTION
Introduction
  • Clinicians treating HIV-infected adolescents should know how to screen adolescents for substance use and, if substance misuse is present, to develop a treatment plan and make referrals as appropriate.
  • Clinicians should be familiar with the stages of substance use progression and patterns of adolescent drug and alcohol use.
Risk Factors 
  • Clinicians should be able to recognize adolescents who are at high risk for substance use.
Communication about Substance Use 
  • Clinicians should convey a nonjudgmental attitude toward adolescents when discussing substance use and should use words and concepts appropriate to the patient’s cultural background and cognitive, linguistic, and emotional development.
  • Clinicians should reassure adolescent patients that discussions regarding substance use are confidential.
History and Screening 
  • Clinicians should obtain a comprehensive history from adolescent patients that includes substance use and mental health screening and psychosocial assessment. Screening should include all levels of alcohol and substance use.
  • Clinicians should screen HIV-infected adolescents for substance use at baseline and every 3 months thereafter. If the HIV-infected adolescent’s initial drug screening result is positive, or if the patient has a history of substance use, the clinician should re-evaluate the patient’s drug use more frequently as needed.
  • As part of the history-taking process, clinicians should incorporate selected brief screening instruments and discuss the confidentiality of screening with HIV-infected adolescents. The chosen screening instruments should be individually tailored for optimal use at baseline and follow-up visits and adjusted for the patient’s substance use history.
Intervention Strategies 
  • Clinicians should use harm-reduction principles for adolescents who are not ready, or not willing, to make abstinence a goal. Such harm-reduction strategies include counseling adolescents to reduce harmful use, such as binge drinking, heavy or daily marijuana use, and polydrug use, as well as referring injection drug-using adolescents and young adults to syringe exchange programs.
  • Clinicians should implement brief interventions for HIV-infected adolescents when a problem with substance use is identified.
  • Clinicians should refer injection drug-using adolescents for opioid-dependence treatment or more intensive levels of care as appropriate, such as extended counseling and case management.
Mental Health Treatment
  • HIV-infected adolescents with co-occurring substance use and mental health diagnoses should be carefully assessed for psychotropic management of their mental health diagnosis.
Referrals for Substance Use Treatment 
  • Clinicians should have access to experienced case managers who can address the multiple disciplines involved in working with HIV-infected substance-using adolescents.
  • Clinicians should recognize that many adolescents do not know about substance use intervention services or how to access them.
  • With the patient’s consent, substance use programs should make every effort to involve the adolescent’s family and supportive adults in their care when appropriate.
  • Substance use programs and HIV care providers should collaborate in the development of treatment plans for adolescents who are engaged in both types of care.
Maintaining Care 
  • Clinicians should ensure that HIV-infected adolescents are engaged in medical care regardless of whether or not they are actively using drugs.
  • Clinicians should include substance-using HIV-infected adolescents in the medical treatment planning process as early as possible.
Relapse Prevention
  • Clinicians should coordinate with relapse prevention programs and mental health care providers when caring for HIV-infected adolescents with a history of substance or alcohol dependence.
  • Clinicians should ask HIV-infected adolescents in early recovery at each visit about the date of last use of substances, alcohol, and tobacco.

Care of Female Adolescents | with HIV Infection Guideline

Introduction

Subcommittee on the Care of Adolescents with HIV Infection, March 2007 

RECOMMENDATION
  • Clinicians should identify a supportive adult to whom the adolescent can safely disclose HIV-related information and discuss reproductive health issues.

This guideline includes recommendations for identifying HIV-infected adolescents; obtaining a baseline medical history; performing baseline and ongoing physical examinations, laboratory evaluations, and psychosocial interventions; and maximizing treatment adherence. This chapter discusses issues that may have particular diagnostic, preventive, or therapeutic implications for female adolescents, including epidemiology, pelvic examinations, reproductive health, contraception, and pregnancy.

Acquisition of HIV: The most common mode of female HIV acquisition is through heterosexual sex. In New York State, female adolescents aged 13 to 24 accounted for 42% of the adolescents living with HIV/AIDS in 2005 [1]. Nationwide, it is estimated that 63% and 82% of new AIDS cases among younger (13 to 19 years) and older (20 to 24 years) adolescent females, respectively, are from heterosexual transmission [2].

Sexually active adolescent females may be particularly vulnerable to acquiring HIV infection for the following reasons [3]:

  • An adolescent’s immature cervix contains more single-layer columnar cells that may be more vulnerable to infection.
  • Females are more likely than males to experience asymptomatic STIs, and the presence of STIs may enhance transmission of HIV infection.
  • HIV infection is more easily transmitted from male to female than female to male because 1) the susceptible surface area of the female (cervical epithelium and the mucosal area of the vagina and rectum) is larger than that of the male (urethral meatus) and 2) semen can remain in the vagina, cervix, and rectum for hours to days after sexual intercourse, making the period of HIV exposure much longer for a female than a male.

Identifying a supportive adult: HIV infection and reproductive health issues are often difficult topics for many HIV-infected adolescents to discuss. Some adolescents are comfortable discussing these subjects with parents/guardians, while others are not. A supportive adult with whom the adolescent can comfortably discuss HIV-related information and reproductive health care should be identified. The medical team should encourage the adolescent to involve this person in discussions concerning her care. This person may or may not be a parent or legal guardian but should be someone with whom the adolescent feels comfortable sharing personal information.

References:
  1. NYSDOH. NYS HIV/AIDS surveillance semiannual report for cases diagnosed through 2005. Available at: http://www.health.state.ny.us/diseases/aids/statistics/semiannual/2005/surveillance_semiannual_report_2005_june.pdf
  2. Kaiser Family Foundation. Women and HIV/AIDS in the United States. HIV/AIDS Policy Fact Sheet. February 2006. Available at: http://www.kff.org/hivaids/upload/6092-03.pdf
  3. Futterman D. HIV and AIDS in adolescents. Adolesc Med Clin 2004;15:369-391. Review.

HPV Vaccine

March 2007

RECOMMENDATIONS
  • Clinicians should offer the HPV vaccine to HIV-infected females between the ages of 9 and 26 years.
  • Clinicians should continue to obtain cervical Pap tests on the recommended schedule in HIV-infected women who have been vaccinated with HPV vaccine. Vaginal and vulvar visual inspection should be continued at regularly scheduled pelvic examinations.
  • HPV typing prior to administering the vaccine is not recommended.

In June 2006, the Food and Drug Administration (FDA) approved the release of a quadrivalent HPV vaccine (Gardasil) that protects against disease caused by HPV types 6, 11, 16, and 18. These HPV types are associated with 70% of cervical cancers (HPV 16 and 18) and 90% of genital warts (HPV 6 and 11) in non-HIV-infected women [1]. The pivotal clinical trials showed that the vaccine prevented precancerous vulvar, vaginal, and cervical lesions caused by these HPV types for up to 36 months. Most studies have shown a high prevalence of HPV infections in HIV-infected individuals [2].

Administration: The vaccine is FDA-approved for administration to females between the ages of 9 and 26 years [3]. It is administered as a three-dose regimen over a 6-month period (0, 2, and 6 months). The full regimen must be completed to confer protection. HPV vaccine has been demonstrated to provide high levels of neutralizing antibody for 5 years; the full length of its protection has not been established.

Vaccine is for prevention, not treatment: The HPV vaccine is preventive, but not therapeutic. Current studies demonstrate that the preventive efficacy of the HPV vaccine is greatest in women who are not yet sexually active and thus have not been exposed to HPV. However, HPV testing is not required before administration of the vaccine, and most women, regardless of sexual activity status, may benefit from vaccination. In the pivotal clinical trials, only 1 in a 1,000 women showed evidence of having been exposed to all four types of HPV prevented by the vaccine. Gardasil may also provide some cross-protection against HPV genotypes other than 6, 11, 16, and 18. However, additional data are required before the vaccine can be recommended for the prevention of cross-reactive HPV types.

Safety and efficacy: Most of the data regarding HPV vaccine safety and efficacy are derived from studies in non-HIV-infected females. HIV-infected women may have reduced antibody response to the immunization because women who are immune suppressed have an impaired ability to mount an immune response. Studies are currently underway to provide more extensive data regarding the safety and efficacy of the vaccine in the HIV-infected population. There currently are no recommendations to vaccinate males against HPV.

Ongoing cervical screening: Clinicians should continue to perform regular cervical screening with Pap tests and visual inspection of the vulva and vagina during annual pelvic examinations in women who have received the HPV vaccine because the vaccine does not protect against the 25% to 30% of lesions and genital cancers caused by other HPV types. Females who have not engaged in vaginal or anal penetrative sex but who have participated in sexual activity with direct genital contact should be evaluated for vulvar lesions because the virus can be passed through direct contact.

References:
  1. Centers for Disease Control and Prevention. Quadrivalent Human Papillomavirus Vaccine – Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56:1-24. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr56e312a1.htm
  2. Clifford GL, Goncalves MA, Franceschi S for the HPV and HIV Study Group. Human papillomavirus types among women infected with HIV: a meta-analysis. AIDS 2006;20:2337-2344.
  3. Food and Drug Administration. Gardasil. Available at: http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM094042

Sexual Risk Assessment and Risk-Reduction Counseling

March 2007

RECOMMENDATIONS
  • Clinicians should obtain a sexual risk assessment during the baseline examination and during routine visits.
  • The clinician should routinely discuss sexuality, personal relationships, birth control, safe sex, and partner disclosure with patients. Clinicians should discuss partner disclosure prior to the onset of the adolescent’s sexual activity.
  • Clinicians should inquire about physical and sexual abuse and sexual assault and should refer patients for counseling when indicated.
  • Clinicians should recommend consistent and correct use of latex condoms to prevent pregnancy, acquisition of STIs, transmission of HIV/STIs, and superinfection. For patients with a latex allergy, clinicians should recommend polyurethane condoms. Clinicians should advise HIV-infected adolescents to avoid using lambskin condoms or condoms that are lubricated with nonoxynol-9. For adolescents with same-sex partners, the use of dental dams during oral sex and safe use of sex toys should be discussed to prevent disease transmission.
  • Clinicians should use a model to demonstrate to adolescents the correct way to use a condom.
  • Clinicians who are not comfortable discussing sexual practices with adolescents should consult with clinicians who have experience in risk-reduction counseling for adolescents or seek training to enhance their comfort level.

Sexuality and sexual practices should be addressed during the initial visit and during routine clinical visits. Adolescents may choose not to disclose all important personal information during the first visit. Some adolescents are comfortable discussing sexual activity and reproductive health with their providers with whom they have had a long-term relationship, in some cases since childhood; however, other adolescents may feel more comfortable discussing their sexual activity with a different provider or a same-sex provider. Clinicians who are nonjudgmental when interacting with patients may establish a trusting bond with the adolescent which will facilitate discussion of sensitive issues.

The purpose of the sexual history and risk behavior assessment is to enable the clinician to provide appropriate risk-reduction counseling. This counseling should include safer-sex practices, including strongly advising continued use of condoms to prevent superinfection with an HIV-infected partner or transmitting HIV/STIs to their sexual partners. Clinicians who are not comfortable discussing different sexual behaviors and ways to reduce the risk of sexually transmitting HIV should seek training to enhance their comfort level. Consultation with clinicians who have experience in risk-reduction counseling for adolescents may also be beneficial.

Elements of a Sexual Risk Assessment

  • Is patient is sexually active or does she have plans to initiate sexual activity?
  • Age at initiation of sexual intercourse
  • Number of sexual partners
  • Gender(s) and ages of partners and length of relationships
    • Inquiring about the age of partners may be useful because it is often more difficult for younger women to be assertive regarding safe-sex practices with older partners.
  • HIV and STI status of partners
  • Disclosure to partner(s) of HIV status: If HIV status has not yet been disclosed to partner(s), the clinician should offer assistance.
  • History of STIs and treatment
  • Sexual practices (oral, anal, vaginal, digital, use of sex toys) with and without protection
  • Contraceptive history and current practices, specifying frequency and condom use
  • Self-assessment of safer-sex practices
  • Pregnancy history
  • Sexual abuse (personal or family)
  • History of exchanging sex for housing, food, money, or drugs
  • Drug or alcohol use

Substance use: Use of alcohol and marijuana is significant among HIV-infected adolescents. Although their use is not a direct risk for HIV transmission, they cause disinhibition which can result in sexual risk taking. Intoxication from these substances impairs the adolescent’s judgment and ability to negotiate condom use and sexual activities with partners. This not only increases the risk of pregnancy and other STIs, but also increases the risk of transmitting HIV infection. Referrals should be made for counseling for patients who indicate risky substance use.

For further information about female substance users, see Care of the HIV-Infected Substance-Using Woman. 

Performing a Gynecologic Examination

March 2007

RECOMMENDATIONS
  • At baseline and as part of the annual comprehensive physical examination, clinicians should obtain a menstrual, gynecologic, and sexual history as well as examine the external genitalia, anus, perineal area, breasts, and axilla using the Tanner rating scale for sexual maturity.
  • The clinician should educate the patient about the importance of periodic pelvic examinations, STI screening, and Pap tests.
  • Clinicians should perform the first gynecologic examination when any of the following occur:
    • Patient reports sexual activity;
    • Patient requests a pelvic examination;
    • Patient presents with any gynecologic symptom for which a pelvic examination would assist in a differential diagnosis, e.g., pelvic pain or new onset menstrual irregularity;
    • Patient presents with symptoms of an STI or sexual activity;
    • Patient reaches age 14; however, if the inspection reveals an intact hymen or no likely sexual activity, the speculum examination and the Pap test should be deferred until age 18 or until the patient is sexually active, whichever occurs first.
  • Before performing a first-time pelvic examination in a patient, the clinician should explain the various steps and components involved in the examination, including a review of basic genital anatomy, the instruments used for the examination, and the purpose of the examination. Clinicians should use the smallest speculum available for a first-time examination, even in sexually active adolescents.
  • Patients should be asked if they would prefer having a female provider perform the examination. During the examination, an additional female member of the medical staff should be present as a chaperone.
  • Primary care clinicians who do not directly provide gynecologic care should obtain a menstrual, gynecologic, and sexual history and then refer the patients to gynecologic providers with experience providing examinations to adolescents.

First or Baseline Gynecologic Exam

Adolescent or young adult female patients who have not had a previous gynecologic examination, who have had previous “bad experiences” with pelvic examinations, or who are victims of past sexual assault may require extra time and explanation during their first examination. More than one visit may be necessary for these patients before a comprehensive gynecologic examination can be completed.

New York State Law
Clinicians are required to report cases of suspected child abuse or neglect to the New York State Central Registry at 1-800-635-1522. 

If the clinician is performing the patient’s first pelvic examination, he/she should take time to explain the various steps and components involved in a pelvic examination, show the patient the instruments that will be used, and explain how the instruments function. Well-informed patients may feel more comfortable during examinations, which may then encourage the patient to be proactive in obtaining future routine pelvic examinations. The use of demonstration models or pictures can alleviate concerns about what to expect during a pelvic examination.

The smallest speculum available should be used for a first-time examination, even in sexually active adolescents. For some adolescents, a nasal speculum may be needed.

KEY POINT
Because adolescents may require additional time during clinical visits to become comfortable with the idea of receiving a pelvic examination, it may be necessary to schedule longer appointments.

Evaluation of Sexually Active Female Adolescents

RECOMMENDATIONS
  • At baseline and as part of the annual comprehensive physical examination, clinicians should examine the anogenital area, including the vulva and vagina, to assess for visible ulcerative lesions.
  • Clinicians should perform the laboratory tests listed below for HIV-infected females who are sexually active.

Laboratory Tests for Sexually Active Female Adolescents with HIV Infection

Cervical Pap test: Baseline; 6 months after baseline; then annually, as long as results are normal

  • Colposcopy should be performed for all HIV-infected women with abnormal Pap tests. Follow-up would then vary on a case-by-case basis. Abnormal Pap tests should be repeated every 3 to 6 months thereafter until there have been two successive normal cervical Pap tests. Women with cervical HSIL also should be referred for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
  • Annual anal cytology should be obtained from patients with a history of anogenital condyloma or abnormal cervical/vulvar histology.

Culture, nucleic acid amplification test (NAT), or urine test for gonorrhea: Baseline and every 6 months

  • Urine screening should not preclude performing a pelvic examination because other visible STI lesions may be missed (HPV, HSV, etc.).
  • Depending on the sexual behaviors reported or suspected, oral and anal cultures may be indicated as well as cervical or urethral cultures.

RPR or VDRL for syphilis: Baseline and at least annually

  • Positive test verified by confirmatory FTA-Abs or MHA-TP. Immunofluorescence or DNA amplification test for chlamydia: Baseline and every 6 months

Urine testing for chlamydia: At 6-month evaluations when pelvic exam is not performed

Herpes simplex virus serology: Baseline

Herpes culture: When symptoms are present

Pregnancy test: Baseline and when: 1) upon patient request; 2) change in menses pattern or flow; 3) when timing of unprotected sex is of concern to patient or care provider; or 4) prior to initiation of teratogenic medication (e.g., efavirenz)

Contraception

March 2007

RECOMMENDATIONS
  • Clinicians should counsel patients about contraceptive options. If necessary, patients should be referred to a family planning provider for contraceptive counseling.
  • Clinicians should recommend the simultaneous use of a condom and an additional method of contraception (dual method use) in the event of condom breakage or slippage.
  • When prescribing hormonal contraceptives, clinicians should consider, on a case-by-case basis, drug interactions between HIV-related medications and hormonal contraceptives, the patient’s adherence patterns to medications, and the side effect profile of the hormonal contraceptives. Clinicians should also reinforce the importance of using condoms in addition to hormonal contraception.
  • Clinicians should counsel HIV-infected adolescents about the interactions between ARV medications and oral contraceptives, specifically lopinavir/ritonavir, nelfinavir, nevirapine, ritonavir, saquinavir, and tipranavir, because contraception protection may be reduced.
  • Clinicians should strongly recommend the use of contraception for HIV-infected adolescent females of childbearing age who are receiving efavirenz or combination pills containing efavirenz.

Rates of unintended pregnancy are higher among adolescent and young adult females than among older females; therefore, it is essential that clinicians clearly address reproductive health issues and contraception with HIV-infected adolescents.

Clinicians prescribing contraceptives should be cognizant of adolescent adherence patterns, which may be poor. Many adolescent healthcare clinicians offer younger patients contraception in the form of a shot (Depo-Provera), vaginal ring (Nuvaring), or patch (Ortho-Evra) to reduce inconsistent contraceptive use, which may be encountered with oral contraceptives. However, use of any hormonal contraception is often accompanied by a decrease in use of condoms during sex. Patients should be strongly advised to continue using condoms simultaneously with hormonal contraceptives to avoid superinfection with an HIV-infected partner or transmitting HIV/STIs to their sexual partners.

KEY POINT
Correct and consistent use of routine contraception may be challenging for adolescents. A reliable contraceptive method that does not require daily use may be more successful in this population.

Injectable progesterone (depot medroxyprogesterone acetate, Depo-Provera) is an efficacious contraceptive; however, current data suggest that Depo-Provera can cause bone demineralization when used for prolonged periods. For this reason, the Food and Drug Administration recommends that providers limit the use of Depo-Provera to 2 continuous years followed by an interruption of its use [1]. Recent data suggest that after 2 years of discontinued use of Depo-Provera, bone mineral density returns; however, these studies have not been performed in adolescents with or without HIV infection.

If efavirenz is used, or combination pills containing efavirenz, female adolescents should be informed of the possible risk to an unborn fetus and should be strongly advised to use effective birth control or choose an alternative medication. Many HIV providers prefer not to use efavirenz in this population because of teratogenicity concerns; efavirenz is contraindicated during the first trimester of pregnancy.

RESOURCE
Reference: 
  1. Food and Drug Administration. Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection. November 17, 2004.

Reproductive Health Counseling

March 2007

RECOMMENDATIONS
  • Clinicians should provide reproductive health counseling to HIV-infected female adolescents (described below). As part of reproductive health counseling, clinicians should educate female adolescents about the importance of maintaining their own health should they wish to become pregnant in the future.
  • Clinicians should recommend prenatal vitamins and folic acid for adolescents who wish to become pregnant or who are not taking action to prevent pregnancy.
  • For patients of childbearing age, clinicians should discuss the following concerning ARV medications:
  • Efavirenz and combination pills containing efavirenz should be avoided in adolescents of childbearing age and adolescents who are in their first trimester of pregnancy. These patients should receive an alternative regimen if possible.
    • If there are no alternatives for efavirenz, clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiation.
    • If pregnancy is discovered during the second trimester, an alternative regimen should be offered but can be continued if the benefits outweigh the risks.
    • For adolescents receiving efavirenz and expressing a desire to have children, efavirenz should be discontinued 2 months before stopping contraception.
  • Amprenavir oral solution is contraindicated.
  • Stavudine/didanosine combination should be avoided and only be used when no other combinations are feasible (See Management of HIV-infected Pregnant Women Including Prevention of Perinatal Transmission for more information)
  • Nelfinavir should not be given to pregnant adolescents or to those who anticipate pregnancy, if other treatment options are available. In pregnant adolescents receiving nelfinavir, nelfinavir should be substituted for another ARV agent.
  • Clinicians should consider pregnancy in all adolescents of childbearing age when prescribing medications that are known to be harmful to the fetus. Selection of drugs for the ARV regimen should be guided by available data.

Upon learning of their HIV infection, many HIV-infected adolescents think that they may not live long enough to bear children or may never be able to bear non-HIV-infected children. Many young women view pregnancy as a “rite of passage” and may feel deprived of this “rite.” Perinatally infected female adolescents may develop strong desires to become pregnant in an effort to be connected to a family of their own or to be “normal.” Their motivations may be to be like their peers or, as a result of their fear of mortality; they may want to have children to leave behind in the event of their own premature death.

KEY POINT

Clinicians providing HIV care to adolescents may be the only source of medical information for these patients. Female adolescents may not be as successful as older women in navigating the healthcare system to obtain reproductive health care and information. See Physicians for Reproductive Health: Teen Reproductive Health for additional information.

Clinicians providing HIV care to younger female patients need to proactively counsel patients about future reproductive options. Explicit guidance about how to increase the chances of delivering a healthy, non-HIV-infected infant when the patient is ready to become pregnant should be outlined during this counseling. Topics such as those shown below should be discussed. For patients who are already receiving ARV medications, adherence to the drug regimen should be emphasized. The clinician also should explain to the patient that a planned pregnancy which occurs when the patient is in her best physical condition is one that has the greatest chance of resulting in a healthy, non-HIV-infected infant and a healthy mother.

Elements of Reproductive Health Counseling

General concerns:

  • Effect of HIV on pregnancy
  • Effect of pregnancy on HIV
  • Future reproductive concerns and options

Contraception:

  • Routine contraception and use of dual contraceptive methods
  • Emergency contraception
  • Effect of antiretroviral drugs on oral contraceptive pills

Antiretroviral medications:

  • Potential for maternal and fetal/neonatal toxicity
  • Effect on pregnancy outcome
  • Role in preventing perinatal transmission
  • Importance of adherence to the ARV regimen, especially for patients already receiving ARV medications

Routine prenatal care:

  • Vitamin and folic acid supplementation
  • Smoking cessation
  • Healthy nutrition

Perinatal HIV transmission

  • Risk of transmission and risk-prevention
  • Mode of delivery (cesarean vs vaginal)
  • Avoiding breastfeeding

Parenting responsibilities

  • Housing and food
  • Childcare
  • Medical and pediatric care
  • Continuing education

Providing Care for Pregnant Adolescents

March 2007

RECOMMENDATIONS
  • Clinicians should consider the likelihood of pregnancy when selecting specific ART medications for HIV-infected adolescents because some adolescents may not inform the clinician about a pregnancy for significant periods of time.
  • Clinicians should discuss options with patients who are making decisions about carrying pregnancy to term or terminating pregnancy. For adolescents who are not comfortable discussing pregnancy with their long-term provider, other trained professionals should be accessible.
  • Clinicians should educate pregnant adolescents who choose to carry pregnancy to term about the role of ARV therapy in optimizing maternal health and reducing the likelihood of perinatal transmission.
  • Clinicians should use the three-part zidovudine regimen for all HIV-infected pregnant adolescents, regardless of whether or not they are receiving HAART, unless a specific contraindication to zidovudine is known, such as a history of a severe adverse effect of zidovudine, severe anemia, or the need for an antagonistic medication such as stavudine.
  • The clinician should consult with an HIV Specialist to devise prenatal HAART regimens for perinatally infected adolescents.
  • Primary care clinicians should have referral agreements with obstetrical services that can provide care to HIV-infected females during pregnancy.
  • Clinicians should refer adolescent patients to supportive services available at prenatal clinics.
  • The adolescent’s clinician should work in conjunction with the infant’s pediatrician to provide the adolescent with access to training to improve parenting skills and other necessary services.

Pregnancy is often the time when heterosexually infected females are identified as being HIV-infected. The recommendation for universal counseling with recommended testing of all pregnant women, either prenatally or through expedited perinatal testing, has facilitated the identification of HIV infection in adolescents who become pregnant.

Optimal care of HIV-infected pregnant adolescents includes ARV treatment to reduce mother-to-child HIV-1 transmission and maintenance of general health for the pregnant adolescent. Providers face the difficult task of maximally suppressing the virus while avoiding or minimizing potential toxicities to the mother and fetus. To prevent perinatal HIV transmission, a three-part zidovudine regimen is recommended for all HIV-infected pregnant women, regardless of whether or not they are receiving ART, unless a specific contraindication to zidovudine is known, such as a history of a severe adverse effect of zidovudine, severe anemia, or the need for an antagonistic medication such as stavudine. Factors associated with higher rates of transmission include ruptured membranes for more than 4 hours, advanced maternal disease, high maternal viral load, low maternal CD4 cell count, and concomitant infections, including hepatitis C. Cesarean delivery prior to the onset of labor and ruptured membranes can significantly reduce the risk of transmission. Guidelines for the use of ART during pregnancy, routine monitoring of HIV-infected pregnant women, and labor and newborn management are included in Management of HIV-Infected Pregnant Women Including Prevention of Perinatal HIV Transmission.

KEY POINT
Although HIV-infected pregnant adolescents will be referred to obstetrical care services that can provide care to HIV-infected pregnant women, the clinician may want to remain the primary care provider for the adolescent during the pregnancy.

Clinicians should consider the likelihood of pregnancy when considering specific HAART medications, such as efavirenz or combination pills containing efavirenz, because some adolescent patients may be pregnant for a significant amount of time without informing their HIV providers. Devising prenatal ART regimens for pregnant, perinatally infected females is often difficult because the patients are frequently more advanced in their clinical disease state and may be resistant to many ARV medications. Clinicians should consult with an HIV Specialist when developing a prenatal ART regimen for this population. Treatment during adolescent pregnancy raises multiple issues and should be provided by a clinician experienced in caring for HIV-infected pregnant patients.

Pregnant adolescents may benefit from supportive services to help prepare them for parenthood. Adolescent patients should be referred to supportive services that are often provided at prenatal clinics that encourage a healthy outcome for adolescent patients during their pregnancy and delivery. Supportive services may include prenatal, postpartum, and infant development education; nutrition education for mother and child; parenting skills training; child care support; and counseling, whether group or individual.

RESOURCE
CDC Reproductive Health: Teen Pregnancy

All Recommendations

Subcommittee on the Care of Adolescents with HIV Infection, March 2007

ALL RECOMMENDATIONS: CARE OF FEMALE ADOLESCENTS WITH HIV INFECTION
 Identifying a Supportive Adult
  • Clinicians should identify a supportive adult to whom the adolescent can safely disclose HIV-related information and discuss reproductive health issues.
HPV Vaccine 
  • Clinicians should offer the HPV vaccine to HIV-infected females between the ages of 9 and 26 years.
  • Clinicians should continue to obtain cervical Pap tests on the recommended schedule in HIV-infected women who have been vaccinated with HPV vaccine. Vaginal and vulvar visual inspection should be continued at regularly scheduled pelvic examinations.
  • HPV typing prior to administering the vaccine is not recommended.
Sexual Risk Assessment and Risk-Reduction Counseling
  • Clinicians should obtain a sexual risk assessment during the baseline examination and during routine visits.
  • The clinician should routinely discuss sexuality, personal relationships, birth control, safe sex, and partner disclosure with patients. Clinicians should discuss partner disclosure prior to the onset of the adolescent’s sexual activity.
  • Clinicians should inquire about physical and sexual abuse and sexual assault and should refer patients for counseling when indicated.
  • Clinicians should recommend consistent and correct use of latex condoms to prevent pregnancy, acquisition of STIs, transmission of HIV/STIs, and superinfection. For patients with a latex allergy, clinicians should recommend polyurethane condoms. Clinicians should advise HIV-infected adolescents to avoid using lambskin condoms or condoms that are lubricated with nonoxynol-9. For adolescents with same-sex partners, the use of dental dams during oral sex and safe use of sex toys should be discussed to prevent disease transmission.
  • Clinicians should use a model to demonstrate to adolescents the correct way to use a condom.
  • Clinicians who are not comfortable discussing sexual practices with adolescents should consult with clinicians who have experience in risk-reduction counseling for adolescents or seek training to enhance their comfort level.
Gynecologic Examinations
  • New York State Law: Clinicians are required to report cases of suspected child abuse or neglect to the New York State Central Registry at 1-800-635-1522. 
  • At baseline and as part of the annual comprehensive physical examination, clinicians should obtain a menstrual, gynecologic, and sexual history as well as examine the external genitalia, anus, perineal area, breasts, and axilla using the Tanner rating scale for sexual maturity.
  • The clinician should educate the patient about the importance of periodic pelvic examinations, STI screening, and Pap tests.
  • Clinicians should perform the first gynecologic examination when any of the following occur:
    • Patient reports sexual activity;
    • Patient requests a pelvic examination;
    • Patient presents with any gynecologic symptom for which a pelvic examination would assist in a differential diagnosis, e.g., pelvic pain or new onset menstrual irregularity;
    • Patient presents with symptoms of an STI or sexual activity;
    • Patient reaches age 14; however, if the inspection reveals an intact hymen or no likely sexual activity, the speculum examination and the Pap test should be deferred until age 18 or until the patient is sexually active, whichever occurs first.
  • Before performing a first-time pelvic examination in a patient, the clinician should explain the various steps and components involved in the examination, including a review of basic genital anatomy, the instruments used for the examination, and the purpose of the examination. Clinicians should use the smallest speculum available for a first-time examination, even in sexually active adolescents.
  • Patients should be asked if they would prefer having a female provider perform the examination. During the examination, an additional female member of the medical staff should be present as a chaperone.
  • Primary care clinicians who do not directly provide gynecologic care should obtain a menstrual, gynecologic, and sexual history and then refer the patients to gynecologic providers with experience providing examinations to adolescents.
Sexually Active Patients 
  • At baseline and as part of the annual comprehensive physical examination, clinicians should examine the anogenital area, including the vulva and vagina, to assess for visible ulcerative lesions.
  • Clinicians should perform the laboratory tests listed below for HIV-infected females who are sexually active.
Contraception
  • Clinicians should counsel patients about contraceptive options. If necessary, patients should be referred to a family planning provider for contraceptive counseling.
  • Clinicians should recommend the simultaneous use of a condom and an additional method of contraception (dual method use) in the event of condom breakage or slippage.
  • When prescribing hormonal contraceptives, clinicians should consider, on a case-by-case basis, drug interactions between HIV-related medications and hormonal contraceptives, the patient’s adherence patterns to medications, and the side effect profile of the hormonal contraceptives. Clinicians should also reinforce the importance of using condoms in addition to hormonal contraception.
  • Clinicians should counsel HIV-infected adolescents about the interactions between ARV medications and oral contraceptives, specifically lopinavir/ritonavir, nelfinavir, nevirapine, ritonavir, saquinavir, and tipranavir, because contraception protection may be reduced.
  • Clinicians should strongly recommend the use of contraception for HIV-infected adolescent females of childbearing age who are receiving efavirenz or combination pills containing efavirenz.
Reproductive Health Counseling
  • Clinicians should provide reproductive health counseling to HIV-infected female adolescents (described below). As part of reproductive health counseling, clinicians should educate female adolescents about the importance of maintaining their own health should they wish to become pregnant in the future.
  • Clinicians should recommend prenatal vitamins and folic acid for adolescents who wish to become pregnant or who are not taking action to prevent pregnancy.
  • For patients of childbearing age, clinicians should discuss the following concerning ARV medications:
  • Efavirenz and combination pills containing efavirenz should be avoided in adolescents of childbearing age and adolescents who are in their first trimester of pregnancy. These patients should receive an alternative regimen if possible.
    • If there are no alternatives for efavirenz, clinicians should strongly advise the use of effective contraception and should obtain a pregnancy test before initiation.
    • If pregnancy is discovered during the second trimester, an alternative regimen should be offered but can be continued if the benefits outweigh the risks.
    • For adolescents receiving efavirenz and expressing a desire to have children, efavirenz should be discontinued 2 months before stopping contraception.
  • Amprenavir oral solution is contraindicated.
  • Stavudine/didanosine combination should be avoided and only be used when no other combinations are feasible (See Management of HIV-infected Pregnant Women Including Prevention of Perinatal Transmission for more information)
  • Nelfinavir should not be given to pregnant adolescents or to those who anticipate pregnancy, if other treatment options are available. In pregnant adolescents receiving nelfinavir, nelfinavir should be substituted for another ARV agent.
  • Clinicians should consider pregnancy in all adolescents of childbearing age when prescribing medications that are known to be harmful to the fetus. Selection of drugs for the ARV regimen should be guided by available data.
Pregnancy Care 
  • Clinicians should consider the likelihood of pregnancy when selecting specific ART medications for HIV-infected adolescents because some adolescents may not inform the clinician about a pregnancy for significant periods of time.
  • Clinicians should discuss options with patients who are making decisions about carrying pregnancy to term or terminating pregnancy. For adolescents who are not comfortable discussing pregnancy with their long-term provider, other trained professionals should be accessible.
  • Clinicians should educate pregnant adolescents who choose to carry pregnancy to term about the role of ARV therapy in optimizing maternal health and reducing the likelihood of perinatal transmission.
  • Clinicians should use the three-part zidovudine regimen for all HIV-infected pregnant adolescents, regardless of whether or not they are receiving HAART, unless a specific contraindication to zidovudine is known, such as a history of a severe adverse effect of zidovudine, severe anemia, or the need for an antagonistic medication such as stavudine.
  • The clinician should consult with an HIV Specialist to devise prenatal HAART regimens for perinatally infected adolescents.
  • Primary care clinicians should have referral agreements with obstetrical services that can provide care to HIV-infected females during pregnancy.
  • Clinicians should refer adolescent patients to supportive services available at prenatal clinics.
  • The adolescent’s clinician should work in conjunction with the infant’s pediatrician to provide the adolescent with access to training to improve parenting skills and other necessary services.

Selected Resources

For Care Providers

October 2016

EDUCATION

AIDS Education Training Center (AETC)

HIV Testing in the Dental Chair: Technical Assistance Manual

Northeast/Caribbean AETC

Resource Library

Centers for Disease Control and Prevention (CDC): Sexually Transmitted Diseases in Adolescents and Young Adults

E-patients.net: Salzburg Statement on Shared Decision Making

New York State Department of Health (NYSDOH):

CEI: IV, HCV & STD Clinical Education Initiative

Emergency Contraception: What You Need to Know

NYS AIDS Institute Training Center

NYS Opioid Overdose Prevention Program

NYSDOH HIV Uninsured Care Programs

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Partner Services: What Health Care Providers Need to Know

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

What to do if You Have Been Raped or Sexually Assaulted

UCSF: HIV InSite

US Department of Veterans Affairs:

Dermatological Manifestations of HIV Image Library

HIV/AIDS Image Library

Oral Manifestations of HIV Image Library

 

GUIDELINES

AHRQ: National Guideline Clearinghouse

AIDSinfo (DHHS guidelines): https://aidsinfo.nih.gov/

CDC HIV/AIDS Guidelines and Recommendations: http://www.cdc.gov/hiv/guidelines/

IAS-USA Practice Guidelines: https://www.iasusa.org/guidelines

 

LAW

NYC Health: Reporting Diseases and Conditions

New York State (NYS): Office for the Prevention of Domestic Violence

NYSDOH:

Communicable Disease Reporting Requirements

Court-Ordered HIV Testing of Defendants

Expedited Partner Therapy: A Guide for Partner Care

HIPAA Information Center

HIV Testing

HIV Uninsured Care Programs: Summary

HIV/AIDS Laws & Regulations

HIV/AIDS Testing, Reporting and Confidentiality of HIV-Related Information

Partner Services: What Health Care Providers Need to Know

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexually Transmitted Diseases

US Courts: courtsystem.org

 

SERVICES

National Institutes of Health (NIH): ClinicalTrials.gov

New York eHealth Collaborative: NYEC

NYC Health:

Life Net

Contact Notification Assistance Program (CNAP)

Expedited Partner Therapy

STD and HIV Services, including Clinic Locations and Hours

NYC Quits

NYS:

Office for the Prevention of Domestic Violence

Office of Victim Services

NYSDOH:

Directory of ESAP Providers in New York State

Expanded Syringe Access Program (ESAP): Overview of Law and Regulations

HIV Testing

HIV Uninsured Care Programs: Summary

New York State PrEP/PEP Provider Voluntary Director

NYS Expanded Syringe Access Program (ESAP)

NYS Opioid Overdose Prevention Program

NYS Safe Sharps Collection Program

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Partner Services: What Health Care Providers Need to Know

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

STD Clinics in New York State

Wadsworth Center

What to do if You Have Been Raped or Sexually Assaulted

 

TOOLS

AIDSinfo: Drug Database

Antiretroviral Pregnancy Registry: For Health Care Providers

HIV Clinical Resource

Mental Health Screening: Quick Reference Guide

Provider Guide to HIV Testing Quick Reference Card

Substance Use Screening: Quick Reference Guide

NYSDOH: CEI: HIV, HCV & STD Clinical Education Initiative

University of Liverpool: HIV Drug Interactions

UCSF HIV InSite: Database of Antiretroviral Drug Interactions

For Consumers

EDUCATION

Advocates for Youth: Respect. Responsibility.

AIDSinfo Fact Sheets (English and Spanish): https://aidsinfo.nih.gov/education-materials/fact-sheets/

AIDSinfo Infographics:

Antiretroviral Therapy . . . What does it do?

HIV and AIDS: What’s the Difference?

HIV and Birth Control

HIV Discordant Couples

HIV Drug Resistance

Living with HIV: Steps to Better Health

Protecting Baby from HIV

What Do My Lab Results Mean?

Three Things to Know about HIV Treatment

Centers for Disease Control and Prevention (CDC): Act Against AIDS

E-patients.net: Salzburg Statement on Shared Decision Making

Fenway Health: Transgender Health

New York State Department of Health (NYSDOH):

Emergency Contraception: What You Need to Know

NYS Opioid Overdose Prevention Program

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

What to do if You Have Been Raped or Sexually Assaulted

UCSF: Center of Excellence for Transgender Health

 

LAW

New York State (NYS): Office for the Prevention of Domestic Violence

NYSDOH:

HIPAA Information Center

HIV Testing

HIV Uninsured Care Programs: Summary

HIV/AIDS Laws & Regulations

HIV/AIDS Testing, Reporting and Confidentiality of HIV-Related Information

Payment Options for PEP Following Non-Occupational Exposures Including Sexual Assault

PrEP and PEP Information & Resources

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

US Courts: courtsystem.org

 

SERVICES

National Institutes of Health (NIH): ClinicalTrials.gov

NYC Health:

Life Net

NYC Quits

STD and HIV Services, including Clinic Locations and Hours

NYS:

Office for the Prevention of Domestic Violence

Office of Victim Services

NYSDOH:

Directory of ESAP Providers in New York State

Expanded Syringe Access Program (ESAP): Overview of Law and Regulations

HIV Testing

HIV Uninsured Care Programs: Summary

New York State PrEP/PEP Provider Voluntary Director

NYS Expanded Syringe Access Program (ESAP)

NYS Opioid Overdose Prevention Program

NYS Safe Sharps Collection Program

Office of Alcoholism and Substance Abuse Services

Office of Mental Health

Provider Reporting & Partner Services

Rape Crisis and Sexual Violence Prevention Program

Sexual Assault Forensic Examiner (SAFE) Program

Sexually Transmitted Diseases

Smokers’ Quitline

STD Clinics in New York State

What to do if You Have Been Raped or Sexually Assaulted

MENTAL HEALTH

The Mental Health Guideline Committee and invited affiliates produced the mental health guidelines

Adherence to ART Guideline

Introduction

Mental Health Guidelines Committee, September 2006

RECOMMENDATION
  • Patients with mental health disorders should be considered candidates for antiretroviral therapy (ART) if they meet the medical eligibility criteria for ART and demonstrate readiness to begin therapy. Clinicians should determine treatment readiness on a case-by-case basis, weighing such factors as whether the patient attends the majority of his/her appointments and whether he/she expresses an interest in receiving ART.

Patients with mental health disorders should be considered candidates for ART if they meet the medical eligibility criteria for ART and demonstrate readiness to begin therapy. Whether a patient is ready to begin therapy needs to be determined on a case-by-case basis; however, factors such as whether the patient attends the majority of his/her appointments and expresses interest in receiving ARV treatment will help to determine whether the patient is ready.

Achievement of the benefits of ART requires careful adherence to regimens that may be complex and/or cause unpleasant side effects. Non-adherence to ART may result not only in reduced treatment efficacy but also in the selection of drug-resistant HIV strains and increased progression to AIDS and death [1,2]. Because the exact level of adherence that is necessary to prevent the emergence of drug-resistant virus or to delay disease progression to AIDS and death is unknown, near-perfect adherence (>90% to 95%) remains the goal for all HIV-infected patients [3,4], including those with mental health disorders or a history of mental health disorders.

Appropriate identification and treatment, or referral for treatment, of underlying mental health disorders will facilitate optimal adherence among this patient population. Depression, the most studied mental health disorder, has been shown to be predictive of poor adherence [5,6]. However, an improvement of depressive symptoms should result in improved adherence [7].

KEY POINT
  • The most effective means of promoting adherence in patients with mental health disorders is through adequate stabilization of their mental health symptoms and integration of mental health treatment into the comprehensive treatment plan.
References:
  1. Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000;14:357-366.
  2. Montaner JSG, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients. JAMA 1998;279:930-937.
  3. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progressions to AIDS. AIDS2001;15:1181-1183.
  4. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: Risk factors for virologic failure and adverse drug reactions.  Ann Intern Med 1999;131:81-87.
  5. Gordillo V, del Amo J, Soriano V, et al. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS1999;13:1763-1769.
  6. Avants SK, Margolin A, Warburton LA, et al. Predictors of nonadherence to HIV-related medication regimens during methadone stabilization. Am J Addict 2001;10:69-78.
  7. Starace F, Ammassari A, Trotta MP, et al. Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2002;3(Suppl 3):S136-S139.

Coordination of Care

September 2007

RECOMMENDATIONS
  • Primary care clinicians should refer patients to licensed mental health providers when:
    • Initial mental health treatment by the primary care clinician is ineffective
    • Complex mental status evaluations become necessary or a patient’s behavior jeopardizes effective treatment
    • The patient has co-occurring mental health and substance use disorders
  • Primary care clinicians and mental health care providers should collaborate to develop a step-by-step treatment plan. The treatment plan should delineate the frequency of follow-up visits with both providers as well as the frequency of team meetings to reevaluate effectiveness of the overall medical and mental health treatment.
  • Primary care clinicians should initially consult with a psychiatrist when managing patients with mental health disorders who refuse mental health care. Throughout the patient’s care, the clinician should communicate with a psychiatrist or a licensed mental health professional who can provide consultation.
  • Primary care clinicians should notify the mental health care provider when there is a change in medical or mental health treatment.

The care for HIV-infected patients with mental health disorders should be a collaborative effort involving patients, primary care clinicians, and mental health providers. Extra attention and involvement of the care team may be required to ensure that these patients adhere to their ARV regimens. When patients are also taking psychotropic medications, adherence may be more difficult, which can make coordination of care even more critical. When necessary, case managers, substance use counselors, relatives, pharmacies, insurance companies, and domestic violence service providers should also be involved.

Regular communication between primary care clinicians and the mental health provider(s) offers a chance to discuss techniques for approaching patients with mental health disorders. For patients who have established a therapeutic alliance with their mental health provider, a meeting involving the patient, the primary care clinician, and the mental health provider can help “transfer” the trust from the mental health provider to the primary care clinician. The same strategy can be used to transfer the trust from the primary care clinician to the mental health provider. This can help the patient feel that the care team takes a genuine interest in the his/her health.

When patients with mental health disorders do not agree to mental health evaluation and treatment by a mental health professional, the primary clinician should establish a “silent partnership” with a licensed mental health professional who can help the primary clinician develop a treatment strategy for the patient. Because psychiatrists are physicians and are familiar with medical illnesses and their treatment, initial consultation with a psychiatrist would be ideal for the primary care clinician to establish the patient’s overall care. A licensed mental health professional may play the primary role as silent partner thereafter. Importantly, however, initiation of or changes in psychotropic
medications should be performed in consultation with a psychiatrist  when necessary.

A mental health patient who is enrolled in a methadone treatment program should be educated about drug-drug interactions because he/she may develop opiate withdrawal symptoms after initiating ARV treatment or other medications. The patient should also be asked to notify the medical staff at the drug treatment program that he/she is initiating ARV treatment. If symptoms occur, adjustment of  methadone dose may need to be made with ongoing coordination between the primary care clinician and the patient’s methadone program.

Predictors and Barriers

September 2006

Predictors

Predictors of adherence that have been consistently identified among persons with HIV infection with and without mental health disorders include the following:

  • Social stability and support
  • Beliefs and knowledge about medications
  • Confidence in their ability to adhere successfully to an ARV regimen
  • A regimen that works (“fits”) with their daily activities [1-3]
  • A strong and trusting patient-provider relationship
KEY POINT
  • Patients with mental health disorders may have learned skills related to adherence to psychiatric medications that they can use to help them adhere to HIV treatment.

Barriers

Adherence to medication regimens, including ARV treatment, has been shown to be affected by mental health and psychosocial factors. Mental health factors that may affect adherence include:

  • Substance use disorders
  • Affective disorders, such as bipolar disorder and depression
  • Anxiety disorders, such as generalized anxiety disorder, panic disorder, post-traumatic stress disorder (PTSD)
  • Fluctuations in mental health status or impairments in cognitive function, which may interfere with a patient’s ability to follow directions
  • Personality characteristics, such as pessimism, apathy, and poor coping styles

Although mental health disorders and/or history of substance use disorders are not contraindications for initiation of treatment, these factors may make adherence more challenging. Active substance or alcohol use is one of the few relatively consistent predictors of poor adherence [4,5]. Patients with severe affective disorders have also been found to have lower rates of adherence. However, it is noteworthy that, at least in one large study, patients with schizophrenia were found to be as adherent to ARV therapy as those without a serious mental health disorder [6].

Psychosocial factors that may affect adherence include:

  • Lack of social support
  • Homelessness
  • Family instability
  • Domestic violence
  • Poor self-image and fears of stigma

Among homeless individuals, adherence may be compromised when they experience increased housing instability or stay in settings not conducive to adherence, such as moving from a residential hotel to a shelter, not having a secure place to keep medications, or not having a refrigerator for certain medications [7].

References:
  1. Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG adherence instruments. AIDS Care 2000;12:255-266.
  2. Safren SA, Otto MW, Worth JL, et al. Two strategies to increase adherence to HIV antiretroviral medication: Life-steps and medication monitoring.Behav Res Ther 2001;39:1151-1162.
  3. Kalichman SC, Ramachandran B, Catz S. Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J Gen Intern Med1999;14:267-273.
  4. Haubrich RH, Little SJ, Currier JS, et al. The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999;13:1099-1107.
  5. Arnsten JH, Demas PA , Grant RW, et al. Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J Gen Intern Med 2002;17:377-381.
  6. Walkup JT, Sambamoorthi U, Crystal S. Use of newer antiretroviral treatments among HIV-infected Medicaid beneficiaries with serious mental illness.  J Clin Psychiatry 2004;65:1180-1189.
  7. Community Health Advisory and Information Network. Report 2004-1: Service Gaps and Utilization in the Continuum of Care in NYC. New York: HIV Health and Human Services Planning Council. Available at: http://www.nyhiv.org/pdfs/chain/CHAIN%202004-1%20Report_Service%20Gaps%20and%20Utilization%20in%20the%20Continuum%20of%20Care%20in%20New%20York%20City.pdf

Identifying and Addressing Potential Barriers

September 2006

RECOMMENDATIONS
  • Clinicians should carefully assess each patient to evaluate his/her ability to adhere to ART.
  • Clinicians should identify and address potential barriers to adherence before initiating ART. If clinicians elect to defer ART while addressing potentially modifiable barriers to adherence, they should discuss this decision with the patient and document it in the medical record.
  • Clinicians should discuss the following with patients before initiating ART:
    • Clinician and patient treatment goals
    • Patient’s concerns about treatment and ability to adhere
    • Potential side effects of ARV therapy and potential interactions with psychotropic and other medications, as well as how the side effects and interactions will be managed should they occur
  • Clinicians should use translator or sign language services when language barriers exist.
  • Primary care clinicians should refer patients with mental health disorders to specialized adherence services when adherence barriers cannot be resolved, particularly if the patient has AIDS or is at risk for advanced progression of HIV.

Determination of a patient’s ability to adhere and promotion of adherence are processes that begin before patients actually start taking medications. Identification and management of potential barriers to adherence before initiating ART in HIV-infected patients with mental health disorders are critical (see Table 1). Clinicians may choose to defer ART while addressing potentially modifiable barriers to adherence. In patients with advanced AIDS, it may be appropriate to initiate ART, even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support (see NYSDOH Linkage, Retention and Treatment Adherence Initiative).

An initial step in the identification and management of barriers to adherence involves a discussion with the patient about his/her treatment goals. Discussions about treatment goals involve the patient in the decision of when to initiate therapy. The clinician should not assume that the patient’s goals are the same as the clinician’s goals. For example, the clinician’s main goal may be viral load suppression, whereas the patient’s main goal may be to look healthier. Discussion points may include the following:

  • If the clinician and patient have different goals, how can they bridge the difference?
  • How realistic are the patient’s goals?
  • Which symptoms might impede him/her in achieving his/her goals?

After discussing treatment goals, the clinician should give the patient the opportunity to discuss his/her concerns about treatment readiness: How hopeful is the patient about adherence to both HIV and psychotropic medications? Some patients may fear the consequences of initiating ART. For example, the patient may be afraid of:

  • The stigma associated with receiving ART
  • Losing government benefits if his/her medical status improves
  • Giving up psychological or material benefits associated with the “sick role”
  • Returning to an anxious state of uncertainty about the length of time that the medications will be effective

By expressing interest in the patient’s concerns and goals, the clinician may both strengthen the patient-provider relationship as well as provide means for supporting HIV treatment adherence. For example, a patient with a history of trauma might be too anxious to put a potentially toxic medication into his/her body. The patient’s commitment to HIV care may be strengthened by the clinician showing an active interest in learning about the patient’s anxiety and related social concerns:

  • Who in the patient’s life is aware and supportive of his/her mental health problems?
  • What kind of experience has he/she had with mental health professionals and psychiatric medications?
  • Does the patient have health beliefs or cultural beliefs about western medicine that are causing additional anxiety about taking medication?

When assessing readiness for treatment in patients with mental health disorders, the factors in Table 1 should be considered as potential barriers.

Table 1: Assessment and Approaches to Potential Barriers to Care
Questions Assessment Possible Approaches
Stage of acceptance Is the patient in denial? Educational approaches; motivational interviewing; medication education support group; consider referral for counseling
Mental health Is there an untreated mental health disorder? Treat the underlying mental health symptoms; refer for treatment; “silent partner” with mental health provider
Cognitive functions Does the patient understand instructions? See Cognitive Disorders Guideline; see “Communication Strategies for Clinicians Treating Patients With Mental Health and/or Substance Use Disorders” (below); see Cognitive-Behavioral Strategies
Language barriers Do the clinician and patient speak the same native language? Is the patient deaf or does the patient have a hearing impairment? Translator or sign language interpreter; someone who does not know the patient may be preferable
Substance use Is there active substance use or inadequate substance use treatment? See Substance Use guidelines
Presence or severity of particular symptoms Are any of the following symptoms present? Helplessness; hopelessness; negativity; lack of motivation; apathy; low energy and easy fatigue; stigma and shame about HIV or mental health disorders; low self-esteem; depression; and inadequate coping styles, especially under stress [1,2]. Treatment adherence support program; screen for common mental health disorders; if symptoms are due to a personality disorder, see Personality Disorders; consider full mental health evaluation
Support network and social stability What is the degree of support from family and friends? Is there lack of social stability (e.g., housing problems, legal issues)? Are children or other dependents in the home? Is there domestic violence? With patient’s consent, consider involving family, friends, HIV social service organization, case management services
History of abuse or violence Does the patient have PTSD symptoms? See Trauma and Post-Traumatic Stress Disorder
Medication concerns Has the patient had poor past experiences handling side effects? Would the regimen “fit” with the patient’s daily routine? Is there a risk of drug-drug interactions? Consider regimen that accommodates lifestyle; avoid regimens with possible side effects that would likely lead to poor adherence

The more disorganized and chaotic a patient’s life is, the more important improved treatment-setting characteristics and supportive services become:

To optimizing the treatment-setting, offer the following:

  • Assurances of confidentiality
  • Incentives to keep appointments, such as food and travel vouchers
  • More frequent follow-up monitoring
  • A comfortable, private, and welcoming clinic setting

Improved waiting time in the clinic, particularly for patients with personality disorders, who often have poor coping skills and a very low tolerance for frustration. Clinicians may consider arranging these patients’ appointments at the beginning of the day or arranging a special “slot” because patients who feel shamed and stigmatized may feel too uncomfortable to wait in an area with other patients. Patients experiencing uncontrollable muscle movement or who have difficulty sitting still for any reason may be disruptive to the waiting area.

Refer patients as needed:

  • To adherence support groups and adherence research projects
  • For food and nutritional supplements
  • To case-management services for assistance in obtaining financial support, housing, and childcare and help with managing the cost or coverage of drugs, medical care, and transportation for traveling to appointments
  • To various services, such as outpatient mental health clinics, HIV adult day programs, psychiatric day programs, mental health residential programs, nutritional programs, stress-management services, and professionally or peer-led support groups

Designated AIDS centers, HIV/AIDS social service organizations, and select pharmacies offer educational programs and support groups designed to help patients with medication adherence. Some programs may target particular issues related to adherence. For example, some target their services to patients who are starting their first ARV regimen (see NYSDOH Linkage, Retention and Treatment Adherence Initiative for resources).

References:
  1. Chesney MA. New antiretroviral therapies: Adherence challenges and strategies. Evolving HIV Treatments: Advances and the Challenge to Adherence, 37th ICAAC Symposium, Toronto, Canada, September 1997.
  2. Singh N, Squier C, Sivek C, et al. Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care 1996:8:261-269.

Initiating, Measuring, and Monitoring ART Adherence

September 2006

RECOMMENDATIONS
  • Clinicians should assess adherence at every routine monitoring visit by verifying that patients are taking the correct medications, correct number of pills per dose, and correct number of doses per day.
  • Clinicians should use finite time intervals when inquiring about and quantifying the patient’s self-report. Clinicians should calculate an average response rate based on information obtained at multiple visits to determine a more accurate estimate of adherence.
  • Clinicians should reassess potential barriers to adherence at least every 3 to 4 months and whenever adherence problems are identified.
  • When clinicians find it necessary to speak with the patient’s friends or family to assess adherence, permission should be obtained from the patient and the patient should be involved in these discussions.

Measurement of adherence is challenging in both clinical and research settings and usually relies on any one or a combination of the following methods:

  • Self-report
  • Pill counts
  • Pharmacy records
  • Electronic pill bottle monitors
  • Therapeutic drug monitoring
  • Computer-assisted self-interview (CASI) assessment

The advantages and disadvantages of each method are discussed in the appendix, Advantages and Disadvantages of Adherence Measures.

When adherence is assessed, finite time intervals should be used. For example, the clinician should ask about the number of doses taken and missed in the past day or past week. Despite its tendency to overestimate adherence, self-report remains the most practical measure in most clinical settings and is most likely to facilitate discussion between patients and providers about the reasons for non-adherence. Self-report is most valid when patients are asked about the number of missed doses within a short time frame (1-7 days), but some studies have found that asking about adherence within the past month is also valid [1,2].

In addition to the usual means of assessing adherence, primary care clinicians may need to involve input from licensed mental health providers, case managers, friends, and/or family members of patients with active mental health disorders. When clinicians find it necessary to speak with the patient’s friends or family to assess adherence, permission should be obtained from the patient and the patient should be involved in these discussions.

As ongoing adherence to treatment is monitored, the factors described in Table 1: Assessment and Approaches to Potential Barriers to Care should be considered.

References:
  1. Walsh JC. Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome. AIDS 2002;16:269-277.
  2. Giordano TP, Guzman D, Clark R, et al. Measuring adherence to antiretroviral therapy in a diverse population using a visual analogue scale. HIV Clin Trials 2004;5:74-79.

Strategies to Improve Adherence

September 2006

Patient-Provider Interaction Strategies

RECOMMENDATIONS
  • Clinicians should encourage patients to state in their own words what they understand about treatment instructions and to ask questions when additional information is needed.
  • Clinicians should encourage patients to be honest by responding in a nonjudgmental, supportive manner when patients report non-adherence.

Factors such as the clinician’s language, eye contact, ability to listen, communication skills, and consultation style can foster or hinder collaboration with the patient. Factors that facilitate the relationship include the provision of understandable information, openness to questions, sensitivity and respect for the patient, interest and trust in the patient, and ongoing availability.

KEY POINT
  • A strong patient-provider relationship, including trust and engagement with the provider, has been associated with improved ARV adherence [1].

Below are communication strategies for the enhancement of adherence in patients with mental health and/or substance use disorders. Interventions work best when they are practical, initiated promptly, and individualized to the patient’s characteristics and needs.

Communication strategies: 

  • Proceed slowly; repeat key points; have patients repeat back instructions in their own words
  • Teach science in simple terms
  • Allow honest reporting of non-adherence
  • Use translator or sign language services when language barriers exist
  • Use pictures and/or written material

When a patient reports non-adherence, the clinician should respond in a way that enhances an open and honest partnership. Clinicians can be supportive by acknowledging that treatment for multiple disorders is challenging because of the increased pill burden and added responsibility and stress of adhering to more than one regimen. Being actively supportive by welcoming the patient’s honesty will mitigate any shame that the patient may feel about his/her poor adherence. The clinician might say, “Everyone has difficulty taking medications. The fact that you sometimes remember to take your pills is great. It will help us understand the best way for you take your pills regularly. So, let’s review when you do remember and when you don’t.”

Health Education Strategies

RECOMMENDATION
  • Clinicians should provide adherence information in an organized manner, both orally and in written form, with easy-to-understand brief statements.

Health educational strategies are most effective when the patient receives information, both orally and in written form, that is well organized and easy to understand. Clinicians should convey education points through the use of brief statements. Important educational topics for clinicians and patients to discuss are given below.

Health education points for enhancing adherence:

  • The treatment regimen and treatment options
  • Drug side effects, with special attention to psychiatric side effects—how to address or avoid
  • Drug-drug interactions—how to determine whether interactions are occurring and what to do about them; which drugs do not have any known risks for or lack of likelihood for drug-drug interactions with prescribed and alternative medications, methadone, recreational drugs, and/or alcohol
  • The importance of treating comorbid disorders, such as mental health and substance use disorders
  • The possible impact of HIV on mental health symptoms

Educational tools can be helpful; yet these should complement and enhance the direct communication and not replace it. These tools need to be tailored to the patient (using lay language or, when applicable, native language). 

Motivational Strategies

Motivational strategies can help to address attitudinal barriers and may include providing psychosocial support and involving family members, partners, and social and community organizations.

A therapeutic treatment style that may be used when exploring issues of ambivalence and conflict regarding adherence is motivational interviewing. Through use of motivational interviewing, the clinician attempts to stimulate change by identifying discrepancies in the patient’s current behavior and the patient’s goals of healthier behaviors. When the patient begins to understand how the consequences of current behavior conflict with personal values, the clinician reflects the discordance back to the patient, until the patient realizes that change is necessary and makes the decision to commit to change. This approach encourages patients to describe their behaviors and develop their own solutions.

For patients who have difficulty tolerating direct communication or who may not be able to identify their own needs, use of motivational interviewing may not be suitable. Direct persuasion and aggressive confrontation are not part of motivational interviewing. With this approach, clinicians do not give advice or directives.

Principles of Motivational Interviewing

Clinicians should understand the underlying principles of motivational interviewing before using it. The four key components of motivational interviewing are shown in Table 2.

Table 2: Key Components of Motivational Interviewing
Component Involves
Expressing empathy Understanding and being aware of and sensitive to the feelings, thoughts, and experiences of another. Accomplished through reflective listening.
Supporting self-efficacy Supporting the patient with the sense that an individual can identify and meet one’s needs and goals.
Avoiding argumentation and rolling with resistance Listening to the patient’s resistance to change. Working collaboratively with the patient to develop his/her input regarding the treatment plan.
Discovering discrepancies Helping patients identify discrepancies between their current behavior and desired future behavior.

Expressing empathy: To gain a better understanding of the patient’s perspective, the clinician actively listens without being judgmental. Through this reflective listening, the clinician may find that the patient is not ready or willing to stop engaging in a particular behavior or to adopt a new behavior. In this case, the initial focus is on building therapeutic rapport and supporting the patient, instead of verbally suggesting change.

Supporting self-efficacy: Self-efficacy refers to a person’s belief in his/her ability to successfully carry out a specific task. The clinician should support the patient’s belief in his/her ability to change by giving the patient examples of positive change and emphasizing the importance of taking responsibility. When the patient feels strong support from the clinician, his/her sense of self-efficacy is enhanced.

Avoiding argumentation and rolling with resistance: Motivational interviewing differs from other approaches to behavior change in that it does not label patients (e.g., “non-compliant” or “difficult”). When faced with a patient’s resistance, it is important for the clinician to allow the resistance to be expressed. Through this process, the clinician reflects the patient’s questions and concerns back to the patient, so that the patient may further examine the possible alternatives to this resistance. The patient then becomes the source of the positive actions that could be taken, does not feel defeated in sharing his/her concerns, and is able to take the risk to express feelings.

Discovering discrepancies: Once patient-provider rapport has been established, the goal is to discover and amplify discrepancies between present and past behavior and future goals. This is achieved through examination of the consequences of continuing an unhealthy behavior and often involves discussing the advantages of adopting a new behavior. The patient will then be able to present the argument for change and begin to realize the need for change.

Motivational Interviewing Approach

The acronym OARS outlines the basic approach to interactions in motivational interviewing:

Open-ended questions invite patients to provide more information than yes or no and will encourage them to explore their own motivators for change. This strategy lets the patient know that the clinician is interested in his/her situation, while allowing the clinician to obtain needed information and insight into the patient’s issues.

Affirmations provide opportunities for clinicians to recognize the patients’ strengths.

Reflective listening helps the clinician identify areas of ambivalence. Reflective listening is often challenging because the clinician may need to form assumptions about the meaning of the patients’ statements in order to articulate them back to the patient. It is particularly important to reflect back any statements that indicate that the patient is motivated to change.

Simple reflections acknowledge the patient’s statements about disagreements, feelings, or perceptions.

Double-sided reflections acknowledge both what the patient has said and the ambivalence.

Amplified reflections reveal the patient’s ambivalence in a slightly exaggerated form.

Summaries will emphasize the main points of the discussion and should capture both sides of the patient’s ambivalence. The summary can also be used to shift focus or direction when the patient is expressing impassible resistance. After the clinician summarizes, he/she should invite the patient to make any corrections.

More resources on motivational interviewing are available from the Motivational Interviewing Network of Trainers (MINT).

Cognitive-Behavioral Strategies

Cognitive-behavioral strategies can be used when mild memory difficulties are present or when the individual feels overwhelmed by the pill-taking challenge. Practical strategies include the following:

  • Simplifying regimens: decrease dosing frequency, decrease number of pills
  • Personalizing drug schedules: tailor treatment to lifestyle, link medications to daily activities
  • Using reminders: written instructions or illustrations, pill boxes, timers, diaries, phone calls from family or friends
  • Using available pharmacy services: pharmacies may call patients to remind them about need for refills, deliver medications, provide professional regimen reviews

If memory deficits are pronounced, after evaluation by a neurologist, the assistance of relatives, home health aides, or visiting nurses should be sought. Before initiating treatment or when switching regimens, a practice run without active medication can help a client feel confident about his/her ability to adhere to ARV therapy.

For more information regarding cognitive impairment among HIV-infected patients, see Cognitive Disorders Guideline.

Directly Observed Therapy

Some medical programs and HIV/AIDS social service organizations have programs that provide ARV directly observed therapy (DOT) for outpatients (see the appendix, Advantages and Disadvantages of Adherence Measures). Although shown to be effective in several non-randomized trials [2,3], published data are limited that compare the efficacy of DOT with other modalities for successful treatment of HIV disease. DOT and modified DOT (MDOT) may facilitate adherence through direct supervision of pill-taking. These programs may also include psychoeducational and social service components, as well as behavioral reinforcements. DOT and MDOT may be the only effective means of ensuring treatment adherence in some patients with severe and persistent mental health illness, those with dual mental health and substance use disorders, and those who are living in unstable and disorganized social conditions.

References:
  1. Bakken S, Holzemer WL, Brown MA, et al. Relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS. AIDS Patient Care STDs 2000;14:189-197.
  2. Stenzel MS, McKenzie M, Adelson-Mitty J, et al. Enhancing adherence to HAART: A pilot program of modified directly observed therapy. AIDS Reader 2001;11:317-328.
  3. Babudieri S, Aceti A, D’Offizi GP, et al. Directly observed therapy to treat HIV infection in prisoners. JAMA 2000;284:179-180.

All Recommendations

Mental Health Guidelines Committee, September 2006

ALL RECOMMENDATIONS: ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-INFECTED PATIENTS WITH MENTAL HEALTH DISORDERS
Introduction 
  • Patients with mental health disorders should be considered candidates for ART if they meet the medical eligibility criteria for ART and demonstrate readiness to begin therapy. Clinicians should determine treatment readiness on a case-by-case basis, weighing such factors as whether the patient attends the majority of his/her appointments and whether he/she expresses an interest in receiving ART.
Coordination of Care 
  • Primary care clinicians should refer patients to licensed mental health providers when:
    • Initial mental health treatment by the primary care clinician is ineffective
    • Complex mental status evaluations become necessary or a patient’s behavior jeopardizes effective treatment
    • The patient has co-occurring mental health and substance use disorders
  • Primary care clinicians and mental health care providers should collaborate to develop a step-by-step treatment plan. The treatment plan should delineate the frequency of follow-up visits with both providers as well as the frequency of team meetings to reevaluate effectiveness of the overall medical and mental health treatment.
  • Primary care clinicians should initially consult with a psychiatrist when managing patients with mental health disorders who refuse mental health care. Throughout the patient’s care, the clinician should communicate with a psychiatrist or a licensed mental health professional who can provide consultation.
  • Primary care clinicians should notify the mental health care provider when there is a change in medical or mental health treatment.
Identifying and Addressing Potential Barriers to Adherence
  • Clinicians should carefully assess each patient to evaluate his/her ability to adhere to ART.
  • Clinicians should identify and address potential barriers to adherence before initiating ART. If clinicians elect to defer HAART while addressing potentially modifiable barriers to adherence, they should discuss this decision with the patient and document it in the medical record.
  • Clinicians should discuss the following with patients before initiating ART:
    • Clinician and patient treatment goals
    • Patient’s concerns about treatment and ability to adhere
    • Potential side effects of ARV therapy and potential interactions with psychotropic and other medications, as well as how the side effects and interactions will be managed should they occur
  • Clinicians should use translator or sign language services when language barriers exist.
  • Primary care clinicians should refer patients with mental health disorders to specialized adherence services when adherence barriers cannot be resolved, particularly if the patient has AIDS or is at risk for advanced progression of HIV.
Initiating, Measuring, and Monitoring Adherence to ART 
  • Clinicians should assess adherence at every routine monitoring visit by verifying that patients are taking the correct medications, correct number of pills per dose, and correct number of doses per day.
  • Clinicians should use finite time intervals when inquiring about and quantifying the patient’s self-report. Clinicians should calculate an average response rate based on information obtained at multiple visits to determine a more accurate estimate of adherence.
  • Clinicians should reassess potential barriers to adherence at least every 3 to 4 months and whenever adherence problems are identified.
  • When clinicians find it necessary to speak with the patient’s friends or family to assess adherence, permission should be obtained from the patient and the patient should be involved in these discussions.
Strategies to Improve Adherence 
  • Clinicians should encourage patients to state in their own words what they understand about treatment instructions and to ask questions when additional information is needed.
  • Clinicians should encourage patients to be honest by responding in a nonjudgmental, supportive manner when patients report non-adherence.
  • Clinicians should provide adherence information in an organized manner, both orally and in written form, with easy-to-understand brief statements.

Anxiety Disorders Guideline

Introduction

Mental Health Guidelines Committee   March 2006

Anxiety is a common symptom in HIV-infected patients. When anxiety symptoms are severe or persistent, patients may have an anxiety disorder. These disorders include panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD) (see Trauma and Post-Traumatic Stress Disorder (PTSD). Among HIV-infected patients receiving medical care, 20.3% have been found to have an anxiety disorder, with 12.3% meeting the criteria for panic disorder, 10.4% for PTSD, and 2.8% having generalized anxiety disorder [1]. Patients with other psychiatric disorders, such as adjustment disorders, major depression, psychosis, or substance use disorders, can also present with significant anxiety. To help patients receive optimal care, clinicians need to be aware of the differences among these specific disorders. Furthermore, patients with histories of anxiety or mood disorders are susceptible to recurrence of anxiety symptoms during the course of HIV illness.

KEY POINT
  • Patients with limited social support may be particularly susceptible to developing anxiety symptoms.
Reference:
  1. Vitiello B, Burnam MA, Bing EG, et al. Use of psychotropic medications among HIV-infected patients in the United States. Am J Psychiatry2003;160:547-554.

Presentation and Diagnosis