ADULT HIV CARE

June 2016

RECOMMENDATIONS 
  • Clinicians should recommend ART for all patients with a diagnosis of HIV infection. (AI)
  • Clinicians should counsel patients with seronegative partners about the reduction of HIV transmission risk when effective ART is initiated and viral suppression is achieved, and should strongly recommend ART for patients with seronegative partners. (AI)
  • Clinicians should evaluate and prepare patients for ART initiation as follows:
    • Discuss risks and benefits of ART with the patient (AIII) (see Counseling and Education Before Initiating ART)
    • Assess patient readiness (AIII)
    • Identify and ameliorate 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.

Results from the START trial [1] and 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. See NYSDOH AIDS Institute guideline: Selecting an Initial ART Regimen.
RESOURCES
 References:
  1. INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015 [Epub ahead of print]. [PubMed]
  2. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360:1897-1899. [PubMed
  3. Wright ST, Carr A, Woolley I, et al. CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts. J Acquir Immune Defic Syndr 2011;58:72-79. [PubMed
  4. Writing Committee for the CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med 2011;171:1560-1569. [PubMed]
  5. Cain LE, Logan R, Robins JM, et al, and the HIV-CAUSAL Collaboration. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: An observational study. Ann Intern Med 2011;154:509-515. [PubMed
  6. The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. CD4 cell count and the risk of AIDS or death in HIV-infected adults on combination antiretroviral therapy with a suppressed viral load: A longitudinal cohort study from COHERE. PLoS Med 2012;9:e1001194. [PubMed
  7. Marin B, Thiébaut R, Bucher HC, et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. AIDS 2009;23:1743-1753. [PubMed]
  8. 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
  9. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, Neaton JH, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355:2283-2296. [PubMed
  10. Ho JE, Deeks SG, Hecht FM, et al. Initiation of antiretroviral therapy at higher nadir CD4+ T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals. AIDS 2010;24:1897-1905. [PubMed
  11. Ho JE, Scherzer R, Hecht FM, et al. The association of CD4+ T-cell count on cardiovascular risk in treated HIV disease. AIDS 2012;26:1115-1120. Epub ahead of print. [PubMed
  12. 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
  13. Tozzi V, Balestra P, Bellagamba R, et al. Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: Prevalence and risk factors. J Acquir Immune Defic Syndr 2007;45:174-182. [PubMed] T
  14. Garvey L, Surendrakumar V, Winston A. Low rates of neurocognitive impairment are observed in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy. HIV Clin Trials 2011;12:333-338. [PubMed
  15. Winston A, Puls R, Kerr SJ, et al. Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: A randomized, controlled study. HIV Med 2012;13:245-251. [PubMed
  16. Ellis RJ, Badiee J, Vaida F, et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 2011;25:1747-1751. [PubMed
  17. O’Connor J, Vjecha MJ, Phillips AN, et al. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial. Lancet HIV 2017; Jan 4. pii: S2352-3018(16)30216-8. [Epub ahead of print]. (PubMed)
  18. Silverberg MJ, Chun C, Leyden W, et al. HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev 2011;20:2551-2559. [PubMed]
  19. Bruyand M, Thiébaut R, Lawson-Ayayi S, et al. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis 2009;49:1109-1116. [PubMed
  20. Guiget M, Boue F, Cadranel J, et al. Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): A prospective cohort study. Lancet Oncol 2009;10:1152-1159. [PubMed
  21. Sigel K, Wisnivesky J, Gordon K, et al. HIV as an independent risk factor for incident lung cancer. AIDS 2012;26:1017-1025. [PubMed
  22. 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
  23. van Lelyveld SFL, Gras L, Kesselring A, et al., on behalf of the ATHENA national observational cohort study. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS 2012;26:465-474. [PubMed
  24. Li X, Margolick JB, Jamieson BD, et al. CD4 T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2011;57:421-428. [PubMed
  25. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994;331(18):1173-80. [PubMed]
  26. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999;354(9181):795-802. [PubMed]
  27. Althoff KN, Gange SJ, Klein MB, et al. Late presentation for human immunodeficiency virus care in the United States and Canada. Clin Infect Dis 2010;50:1512-1520. [PubMed]
  28. Centers for Disease Control and Prevention. Reported CD4+ T-lymphocyte results for adults and adolescents with HIV infection—37 States, 2005–2007. HIV Surveillance Supplemental Report 2010;16(No. 1). Published March 2011. Available at:http://www.cdc.gov/hiv/pdf/statistics_2005_2008_HIV_Surveillance_Report_vol_16_no1.pdf
  29. Centers for Disease Control and Prevention. Diagnoses of HIV infection and AIDS in the United States and dependent areas, 2008. Vol. 20. Atlanta, Ga: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2010. Published June 2010. Available at:http://www.cdc.gov/hiv/pdf/statistics_2008_hiv_surveillance_report_vol_20.pdf

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 [1]. 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 [2]. 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.

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 [3-11]
  • Delay or prevention of immune system compromise [12]
  • Possible lower risk of antiretroviral resistance [13]
  • Decreased risk of sexual transmission of HIV [14-17] (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 [18].)
  • Decreased risk of several severe bacterial infections [19]

DISADVANTAGES of early ART in asymptomatic patients:

  • Potential drug-related reduction in quality of life in otherwise asymptomatic individuals [20-22]
  • Possibility of greater cumulative side effects from ART [23]
  • Possibility for earlier development of drug resistance and limitation in future [24] antiretroviral options if adherence and viral suppression are suboptimal
  • Possibility for earlier onset of treatment fatigue
  • Higher prescription drug costs for the individual
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).

References:
  1. Salzburg Statement on Shared Decision Making. Salzburg Global Seminar, February 7, 2011.
  2. Beach MC, Duggan PS, Moore RD. Is patients’ preferred involvement in health decisions related to outcomes for patients with HIV? Gen Intern Med 2007;22:1119-1124. [PubMed]
  3. INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015 [Epub ahead of print]. [PubMed]
  4. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360:1897-1899. [PubMed
  5. Marin B, Thiébaut R, Bucher HC, et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. AIDS 2009;23:1743-1753. [PubMed]
  6. Ho JE, Scherzer R, Hecht FM, et al. The association of CD4+ T-cell count on cardiovascular risk in treated HIV disease. AIDS 2012;26:1115-1120. Epub ahead of print. [PubMed
  7. Silverberg MJ, Chun C, Leyden W, et al. HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev 2011;20:2551-2559. [PubMed]
  8. When to Start Consortium. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: A collaborative analysis of 18 HIV cohort studies. Lancet 2009;373:1352-1363. [PubMed
  9. HIV-Causal Collaboration. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS 2010;24:123-37. [PubMed
  10. Phillips AN, Gazzard B, Gilson R, et al. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naïve individuals with high CD4 cell count. AIDS 2007;21:1717-1721. [PubMed
  11. Lewden C, Bouteloup V, De Wit S, et al, The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord. All-cause mortality in treated HIV-infected adults with CD4 >500 cells mm3 compared with the general population: Evidence from a large European observational cohort collaboration. Int J Epidemiol 2012;41:433-445. [PubMed
  12. Lewden C, Chene G, Morlat P, et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr 2007;46:72-77. [PubMed
  13. Uy J, Armon C, Buchacz K, et al. Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 2009;51:450-453. [PubMed
  14. 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
  15. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000;342:921-929. [PubMed
  16. Castilla J, del Romero J, Hernando V, et al. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr 2005;40:96-101. [PubMed
  17. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: A prospective cohort analysis. Lancet 2010;375:2092-2098. [PubMed
  18. Politch JA, Mayer KH, Welles SL, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 2012;26:1535-1543. Epub ahead of print. [PubMed]
  19. O’Connor J, Vjecha MJ, Phillips AN, et al. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial. Lancet HIV 2017; Jan 4. pii: S2352-3018(16)30216-8. [Epub ahead of print]. [PubMed]
  20. Erikkson LE, Bratt GA, Sandrström E, et al. The two-year impact of first generation protease inhibitor based antiretroviral therapy (PI-ART) on health-related quality of life. Health Qual Life Outcomes 2005;3:32. [PubMed]
  21. Guaraldi G, Murri R, Orlando G, et al. Severity of lipodystrophy is associated with decreased health-related quality of life. AIDS Patient Care STDs 2008;22:577-578. [PubMed
  22. Burgoyne RW, Tan DH. Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): A balancing act. J Antimicrob Chemother 2008;61:469-473. [PubMed]
  23. Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet 2010;376:49-62. [PubMed]
  24. Barth RE, Aitken SC, Tempelman H, et al. Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. Antivir Ther 2012;17:377-386. [PubMed

Special Considerations

Barriers to Adherence

RECOMMENDATIONS
  • 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)
  • Although ART is recommended for all patients with HIV, the urgency of initiation is increased under the following circumstances:
    • AIDS-defining condition(AI) (see Initiating ART Following Acute Opportunistic Infections, below)
    • 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)
  • 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 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)

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 [1]. These patients should remain under particularly close observation for clinical and laboratory signs of disease progression [2]. ART should be initiated as soon as the patient seems prepared to adhere to a treatment regimen. In patients who or pregnant, or have HIV-related malignancies, HIV-associated nephropathy, symptomatic HIV, older age, severe thrombocytopenia from HIV, chronic hepatitis, or 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.

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 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.

Long-Term Nonprogressors and Elite Controllers

 
  • 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 [3].
  • Elite controllers suppress HIV to low but detectable levels (<50-75 copies/mL) for many years [4].

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 [4]. Another study found higher rates of hospitalizations in elite controllers compared to treatment suppressed patients, particularly for cardiovascular and psychiatric conditions [5]; 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 [6]. 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.

References:
  1. Politch JA, Mayer KH, Welles SL, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 2012;26:1535-1543. Epub ahead of print. [PubMed]
  2. Wallis CL, Papathanasopolous MA, Fox M, et al. Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Antivir Ther 2012;17:313-320. [PubMed
  3. Casado C, Colombo S, Rauch A, et al. Host and viral genetic correlates of clinical definitions of HIV-1 disease progression. PLoS One 2010;5:e11079. [PubMed]
  4. Okulicz JF, Grandits GA, Weintrob, et al. CD4 T cell count reconstitution in HIV controllers after highly active antiretroviral therapy. Clin Infect Dis 2010;50:1187-1191. [PubMed]
  5. Crowell TA, Gebo KA, Blankson JN, et al. Hospitalization rates and reasons among HIV elite controllers and persons with medically controlled HIV infection. J Infect Dis 2015;211(11):1692-702. [PubMed]
  6. Karris MY, Haubrich RH. Antiretroviral therapy in the elite controller: justified or premature? J Infect Dis 2015;211(11):1689-91. [PubMed]

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 [1]. 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 [2-4]. 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 [5-9]. 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).

References:

  1. Zolopa A, Anderson J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: A multicenter randomized strategy trial. PLoS ONE 2009;4:e5575. [PubMed
  2. Blanc FX, Sok T, Laureillard D, et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 2011;365:1471-1481. [PubMed]
  3. Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011;365:1482-1491. [PubMed]
  4. Abdool Karim S, Naidoo K, Grobler A, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med 2011;365:1492-1501. [PubMed]
  5. Lawn SD, Torok ME, Wood R. Optimum time to start antiretroviral therapy during HIV-associated opportunistic infections. Curr Opin Infect Dis 2011;24:34-42. [PubMed]
  6. National Institute of Allergy and Infectious Diseases. Bulletin: HIV treatment study in patients with cryptococcal meningitis ends enrollment early: Higher mortality rate found with early antiretroviral therapy. May 30, 2012. [Bulletin]
  7. Torok ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitis. Clin Infect Dis 2011;52(11):1374-83. [PubMed]
  8. Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014;370(26):2487-98. [PubMed]
  9. Bisson GP, Molefi M, Bellamy S, et al. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis 2013;56(8):1165-73. [PubMed]

All Recommendations

ALL RECOMMENDATIONS: WHEN TO INITIATE ART
  • ART should be recommended for all patients with a diagnosis of HIV infection. (AI)
  • 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)
  • 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 Initiating ART
  • 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)
Special Considerations
  • 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)
  • Although ART is recommended for all patients with HIV, the urgency of initiation is increased under the following circumstances:
    • AIDS-defining condition(AI) (see Initiating ART Following Acute Opportunistic Infections, below)
    • 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)
  • 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 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 Opportunistic Infections
  • 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)
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.

Updates and Changes to this Guideline

5/23/2017

  • Revised recommendation: Update states, with no qualifiers, that ART should be recommended for all patients with a diagnosis of HIV infection. (AI)
  • Revised section theme: Changed “Deferring ART” to “Special Considerations”
  • Added a recommendation to “Special Considerations”: Although ART is recommended for all patients with HIV, the urgency of initiation is increased in patients with an AIDS-defining condition (AI); who are pregnant (AI); who are symptomatic from HIV, including HIV-associated neurocognitive disorder (AII); severe thrombocytopenia (AII); HIV-associated nephropathy (AII); HIV-related malignancies (AII); chronic hepatitis B or C infection; (AII) or who are aged 50 years or older (AII).
  • Revised text to specify the following:  In patients who or pregnant, or have HIV-related malignancies, HIV-associated nephropathy, symptomatic HIV, older age, severe thrombocytopenia from HIV, chronic hepatitis, or advanced AIDS, it is appropriate to initiate ART even if some barriers to adherence are present.