Primary Care Approach

Primary Care Approach

Introduction

Medical Care Criteria Committee, April 2011

RECOMMENDATIONS
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. (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 the NYSDOH AI Selecting an Initial ART Regimen Guideline.

History and Ongoing Assessments

Medical Care Criteria Committee, November 2014

RECOMMENDATIONS
HIV-Related History (November 2014)
  • Clinicians should obtain a baseline and an ongoing HIV-related history according to Table 1. (A1)
  • When obtaining an HIV-related history, clinicians should:
    • Use vocabulary that patients can understand, regardless of educational level (A3)
    • Assess patients’ health literacy* (A3)
    • 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 (A3)
  • Clinicians should stress the confidential nature of discussions regarding sexual history, mental health, and substance use. (A3)
  • 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.
Mental Health and Substance Use Assessment (November 2014)
  • All HIV-infected patients should receive baseline and ongoing assessment for the following: (A1)
    • 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. (A3)
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (A2)

*As defined by the National Network of Libraries of Medicine, 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 through the National Network of Libraries of Medicine. Professional development and training for adult education is available through the Literacy Assistance Center.

New York State Law

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 [Alambuya et al. 2011]. 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 (see the New York State standard consent form). 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 patients with HIV.

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

See the following NYSDOH AI guidelines:

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.

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
  • Gender identity claimed by the patient and the individual’s preferred pronouns
  • Sex assigned at birth
  • Anatomic inventory
  • Surgical inventory

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

Substance Use and Substances

  • Frequency of substance use
  • Usual route(s) of administration
  • 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

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 the NYSDOH AI guidelines:

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?
  • Home healthcare: Does the patient require home healthcare?
  • Gender identity: Which gender does the patient claim and which pronouns are preferred?
  • Legal issues, including end-of-life arrangements, permanency planning for dependent children, immigration status, probation status
  • Coping: How the patient is coping with his/her HIV status

Mental Health and Substance Use Assessment

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, including standardized and validated mental health screening instruments, refer to:

For more information on screening in substance use, including a scripted dialogue for assessing substance use, see NYSDOH AI Screening and Ongoing Assessment Guideline.

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.”

Reference

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

Medical Care Criteria Committee, November 2014

RECOMMENDATION
Baseline and Annual 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.
General Appearance, Vital Signs, and Weight (November 2014)
  • 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).
Pain (November 2014)
  • 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.
Ophthalmologic Assessment and Referral (November 2014)
  • Patients with CD4 counts <50 cells/mm3 should be examined by an ophthalmologist at baseline and every 6 months. (A3)
  • Patients with visual disturbances or unremitting ocular symptoms, regardless of CD4 cell count, should be evaluated by an ophthalmologist. (A3)
  • 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).
Head, Ears, Nose, Mouth, Throat, and Neck (November 2014)
  • 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 (A3)
    • Edentulous patients for intraoral examinations annually, including assessment for denture fit and screening for mucosal lesions including oral cancer (A3)
  • 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.
Genitourinary (November 2014)
  • 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. (A3)
Neuropsychological Examination (November 2014)
  • 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.

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

Table 2: HIV-Related Physical Findings
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 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 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 Note dorsocervical fat pad, masses
Chest and breast Note masses, nipple discharge
Musculoskeletal Note muscle wasting, joint swelling
Genitourinary Perform complete female pelvic examination and female and male genital examination, noting vaginal or penile discharge, ulcers, blisters, warts, tenderness, masses, vaginal dryness, cervical abnormalities
Rectal Perform rectal examination, including visual inspection and digital rectal examination, noting lesions and hemorrhoids.
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: 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: Patients with HIV 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 NYSDOH AI Pain in the Substance User with HIV Guideline.

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, in more clusters, and be more widespread in patients with HIV. 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 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.

Ophthalmologic assessment and referral: 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.

Individuals with HIV may experience icterus due to atazanavir-containing regimens [Bertz et al. 2013], acute hepatitis due to viruses or medications, or cirrhosis due to chronic viral hepatitis or alcohol abuse.

Head, ears, nose, mouth, throat, and neck: 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 patients with HIV 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 individuals with HIV is 2- to 3-fold higher than that of the general population [Rahmanian et al. 2011].

KEY POINT
  • The risk of mortality associated with smoking has been found to be significantly increased among patients with HIV (61.5%) compared with those not infected with HIV (34.2%) [Helleberg et al. 2013].

Evidence also suggests that lung cancer may be increased in HIV infection independent of smoking history [Sigel et al. 2012; Mani et al. 2012; D’Jaen et al. 2010]. 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 [Zhang et al. 2012; Gordin et al. 2008; El-Sadr et al. 2006], as well as lower CD4 counts [Phillips et al. 2008; Lichtenstein et al. 2010] and higher viral load levels [Zhang et al. 2012].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 [Mocroft et al. 2013; Friis-Moller et al. 2010; May et al. 2007]. Older nucleoside reverse transcriptase inhibitors (e.g., zidovudine, didanosine) may cause cardiomyopathy [Frerichs et al. 2002]; however, this effect is rare.

Injection drug users are at increased risk for endocarditis and mycotic pseudoaneurysms [Arora et al. 2001]. 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 [Herreros-Villanueva et al. 2013].

Genitourinary: 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 NYSDOH AI Anal Dysplasia and Cancer Guideline.

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

Neuropsychological examination: HIV-related neurologic changes can occur, even without the neurologic side effects of medications, especially as HIV disease progresses. 

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

References

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]

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]

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]

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]

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]

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]

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]

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]

Herreros-Villanueva M, Hijona E, Bañales JM, et al. Alcohol consumption on pancreatic diseases. World J Gastroenterol 2013;19:638-647. [PubMed]

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]

Mani D, Haigentz M Jr, Aboulafia DM. Lung cancer in HIV infection. Clin Lung Cancer 2012;13:6-13. [PubMed]

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]

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]

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]

Rahmanian S, Wewers ME, Koletar S, et al. Cigarette smoking in the HIV-infected population. Proc Am Thorac Soc 2011;8:313-319. [PubMed]

Sigel K, Wisnivesky J, Gordon, et al. HIV as an independent risk factor for incident lung cancer. AIDS 2012;26:1017-1025. [PubMed]

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]

Dermatologic and Related Complications Associated With HIV

November 2014

Dorsocervical Fat Pad

appendix b-1. dorsocervical fat pad

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credits: Dominic C. Chow, MD, University of Hawaii; Larry J. Day, MD, University of Michigan; Cecilia M. Shikuma, MD, University of Hawaii.

Drug-Related Eruption

Drug-related Eruption

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Folliculitis (Eosinophilic)

Folloculitis (Eosinophilic)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Herpes Simplex

Herpes Simplex

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Herpes Simplex (Genital)

Herpes Simplex (Genital)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Herpes Zoster (Shingles)

Herpes Zoster (Shingles)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Kaposi’s Sarcoma

Kaposi's Sarcoma

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Lipoatrophy (Facial wasting: facial fat loss with deepening of nasolabial fold)

Lipoatrophy (facial wasting)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credits: Dominic C. Chow, MD, University of Hawaii; Larry J. Day, MD, University of Michigan.

Lipoatrophy (Wasting: Fat depletion of leg with prominence of veins and enhanced definition of musculature)

Lipoatrophy (wasting)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credits: Dominic C. Chow, MD, University of Hawaii; Larry J. Day, MD, University of Michigan; Cecilia M. Shikuma, MD, University of Hawaii.

Molluscum Contagiosum

Molluscum contagiosum (a)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Susanne Theresia Duerr, MD, University of Regensburg, Germany; provided courtesy of the Hôpital de Shyria, Rwanda.

Molluscum contagiosum (b)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Onychomycosis

Onychomycosis

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Psoriasis

Psoriasis

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Retinopathy (HIV-Related)

Retinopathy (HIV-related)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Seborrheic Dermatitis

Seborrheic dermatitis (a)

Seborrheic dermatitis (b)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Tinea

Tinea

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Paul A. Volberding, MD, University of California San Francisco.

Vasculitis (Associated With HIV/HCV Co-Infection)

Vasculitis (HIV-HCV coinfection)

Source: US Department of Veterans Affairs, HIV/AIDS Image Library. Credit: Erin Huiras Amerson, MD, and Toby A. Maurer, MD, University of California San Francisco. Reproduced with permission from The International AIDS Society-USA [Top HIV Med 2010;18:16-22].

Laboratory and Diagnostic Testing

Medical Care Criteria Committee, March 2011

RECOMMENDATIONS
Routine Lab Testing (March 2011)
  • Clinicians should order appropriate laboratory assessments and screening tests for managing the care of patients with HIV (see Table 3. Routine Laboratory Testing and Diagnostic Screening). (III)
Virologic Assessment (March 2011)
  • 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)
Immunologic Assessment (March 2011)
  • The CD4 lymphocyte profile should include both the absolute count and percentage. (I)
TB Evaluation (March 2011)
  • 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)
Laboratory Screening for STIs (March 2011)
  • 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).
Cytological Screening (March 2011)
  • 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.
Anal Pap Tests (March 2011)
  • 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)
Table 3: Routine Laboratory Testing and Diagnostic Screening

Virologic and Immunologic 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) andprior 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
  • 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
  • Comments:
    • 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.

Screening for STIs

  • RPR or VDRL for syphilis: Verify positive test by confirmatory FTA-Abs or TP-PA; perform at baseline and at least annually and every 3 months for patients with continued high-risk behavior.
  • Gonorrhea and chlamydia: Screen 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
  • Comments:
    • 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 [Palefsky et al. 2001] 

Cytologic Screening

  • Cervical Pap test: Baseline; 6 months after baseline, then annually as long as results are normal
  • Anal Pap test: For men who have sex with men, any patient with a history of anogenital condylomas, women with abnormal cervical/vulvar history: Baseline and annually
  • Comments:
    • 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
  • Comment: 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
  • Comments:
    • 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.
    • HCV testing should be performed in all pregnant individuals.
Additional Tests
  • Amylase and lipase testing: Baseline
  • Toxoplasma gondii antibody screening: Baseline
  • Varicella antibody screening for adults w/o history of chickenpox: Baseline

The patient’s history may indicate the need for these additional baseline tests.

Virologic assessment: 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.  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 POINTS
  • Regular monitoring of HIV RNA levels remains the most meaningful measure of effective ART. 
  • 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 the NYSDOH AI guideline Virologic and Immunologic Monitoring.

Genotypic 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.

Currently available RNA genotypic assays require a minimum viral load in the range of 500 to 2,000 copies/mL, depending on the assay. 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 NYSDOH AI guideline HIV Resistance Assays).

Immunologic assessment: A decline in absolute CD4 count may occur in some situations, such as after interferon therapy or with chemotherapy for malignancy, 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 fluctuating absolute counts.

Tuberculosis evaluation: 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 [CDC1997]. July 2018: For updated information, see HIV.gov > Latent TB Infection and HIV? CDC Has Updated Recommendations, and MMWR June 29, 2018: Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection

Laboratory screening for STIs: 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.

Cervical Pap test: 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 [Franco et al. 2001].

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; see NYSDOH AI guideline Cervical Screening for Dysplasia and Cancer

Anal Pap test: 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; see NYSDOH AI guideline Anal Dysplasia and Cancer.

References

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]

Franco EL, Duarte-Franco E, Ferenczy A. Cervical cancer: Epidemiology, prevention and the role of human papillomavirus infection. CMAJ2001;164:1017-1025. [PubMed]

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]

Health Promotion and Behavioral Counseling

Medical Care Criteria Committee, March 2007

RECOMMENDATION
Risk Reduction (March 2007)
  • Clinicians should provide routine HIV risk-reduction counseling and behavioral health counseling for HIV-infected patients. (I)
Education on Safer Sex (March 2007)
  • 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)
Substance Use Counseling (March 2007)
  • 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)
Tobacco Use Assessment and Counseling (March 2007)
  • 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.
Reproductive Counseling (March 2007)
  • Clinicians should discuss family planning with patients, including risks to the mother and fetus during pregnancy.
Domestic Violence (March 2007)
  • 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.
Psychosocial Assessment (March 2007)
  • 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)

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 [Schreibman and Friedland 2003].

Table 4: 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 NYSDOH AI Working With the Active User Guideline)
  • 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 
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: 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 [Van Damme et al. 200].

Substance use counseling: The NYSDOH AI guidelines on HIV and substance use contain information on the management of substance use in individuals with HIV. For specific information regarding interactions between illicit drugs and prescription drugs, refer to the NYSDOH AI substance use guideline on Drug-Drug Interactions

Tobacco Use assessment and counseling: 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. For further guidance on smoking cessation, refer to the NYSDOH AI Smoking Cessation Guideline.

Reproductive counseling: 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 [Committee on Pediatric AIDS 2013], should be discussed. Alternative or supplemental family planning methods beyond condom use may also be addressed.

Domestic violence: 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: 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, the problems associated with lipid abnormalities, and potential side effects of medications.

References

Committee on Pediatric AIDS. Infant feeding and transmission of human immunodeficiency virus in the United States. Pediatrics 2013;131;391-396. [PubMed]

Schreibman T, Friedland G. Human immunodeficiency virus infection prevention: Strategies for clinicians. Clin Infect Dis 2003;36:1171-1176. [PubMed]

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

Medical Care Criteria Committee, March 2011

RECOMMENDATIONS
Standard Health Maintenance (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)
Opportunistic Infection Prophylaxis (March 2011)
  • Clinicians should initiate prophylaxis for specific opportunistic infections as indicated in Table 4 and discontinue it as indicated in Table 5. (I)

Standard Health Maintenance

Table 5: Age-Appropriate Screening for Health Maintenance in Patients with HIV
Screening Test Frequency
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 [Agrawal et al. 2005].
  • 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 [Agrawal et al. 2005].

Opportunistic Infection Prophylaxis

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

Table 6: 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 7: 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

See Immunizations for Adults with HIV section.

Reference

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]

Immunizations for Adults with HIV

Medical Care Criteria Committee, April 2018

Purpose of this Document

This compendium of immunization recommendations for adults (≥18 years) with HIV who are not pregnant was compiled by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) to assist clinical practitioners in NYS who provide primary care to adults with HIV. The goal is to present in one easy-to-use document all of the routine vaccinations recommended for adults with HIV by the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), HIV Medicine Association (HIVMA) [AIDSinfo 2017], and the Infectious Disease Society of America [Rubin et al. 2014]. The European AIDS Clinical Society guidelines were also consulted [EACS 2017]. Where a recommendation differs from these source documents, the NYSDOH AI rationale is provided. This document integrates current evidence-based clinical recommendations into the healthcare-related implementation strategies of the Ending the Epidemic initiative, which seeks to end the AIDS epidemic in NYS by the end of 2020.

Immunizations against infectious diseases are a particularly important component of care for individuals with HIV. Immunodeficiency reduces natural defenses to vaccine-preventable diseases in people with HIV and places them at increased risk for disease and for severe disease [Crum-Cianflone and Wallace 2014; Rubin et al. 2014]. However, there is concern that patients with HIV-associated immunodeficiency may not be able to mount and maintain an appropriate immune response to vaccines and may be harmed by live virus vaccines. The strength of the immune response may be lower in patients with more advanced HIV, especially among those with CD4 counts <200 cells/mm3 and/or HIV viral load >200 copies/mL, and shorter in duration than in adults without HIV [Crum-Cianflone and Wallace 2014]. Immunogenicity, vaccine response monitoring, and requirements for additional booster doses for patients with HIV are discussed on pages for individual vaccines.

Development of this document: This reference was compiled by the NYSDOH AI Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

The goal of the Clinical Guidelines Program, established in 1986, is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, hepatitis C virus infections, and sexually transmitted infections and to improve drug-user health and LGBT health throughout NYS. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

The NYSDOH AI Medical Care Criteria Committee is charged with developing evidence-based clinical recommendations for clinicians in NYS who treat adults with HIV. The recommendations in this document, with the exception of one, are the same as those of the CDC/NIH/HIVMA guidelines. This document also discusses published literature related to specific vaccines and the rationale for recommendations for which there is no consensus among the referenced guidelines, no evidence specific to patients with HIV, or new data have been published.

References

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

European AIDS Clinical Society (EACS). Guidelines Version 9.0. 2017 Oct. http://www.eacsociety.org/files/guidelines_9.0-english.pdf [accessed 2018 Mar 27]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Considerations and Contraindications

Medical Care Criteria Committee, April 2018

The tables and accompanying discussion in this section compile recommendations from the Centers for Disease Control and Prevention (CDC), National Institutes of Health, and HIV Medicine Association guidelines on immunization of adults with HIV who are not pregnant, along with vaccination schedules, clinical comments, and sources. The only recommendation in this guideline that was developed by the HIV Clinical Guidelines Program Medical Care Criteria Committee is in the section on zoster vaccination. Table 14 compiles all immunization recommendations into one printable table.

Inactivated vaccines are generally considered safe, although insufficient data exist to rule out rare adverse effects [ACIP 2011; Rubin et al. 2014]. Live, attenuated vaccines are contraindicated for patients with CD4 counts <200 cells/mm3 because of the risk of severe reactions in the setting of immunosuppression [Davis et al. 1977; CDC 1985, 1996; Redfield et al. 1987]. For patients with HIV who have CD4 counts ≥200 cells/mm3, inactivated forms of vaccines, such as polio, influenza, typhoid, and zoster are preferred over the live vaccine options. Live, attenuated vaccines should be administered only when an inactivated version does not exist and when the risk of the disease clearly outweighs the theoretical risk of vaccination.

KEY POINT: USE OF LIVE ATTENUATED VACCINES
  • Patients with CD4 count <200 cells/mm3: The following live, attenuated vaccines are contraindicated: Bacillus Calmette-Guérin; measles, mumps, rubella; oral typhoid; rotavirus*; varicella; yellow fever; zoster.
  • Patients with CD4 count ≥200 cells/mm3Use live, attenuated vaccines only if an inactivated alternative is not available and the risk of disease is greater than the risk of vaccination.

*Patient education: Patients with HIV should avoid handling diapers of infants vaccinated for rotavirus in the previous 4 weeks and all household members should wash their hands after changing diapers of an infant recently vaccinated for rotavirus.

Transient increases in viral load and decreases in CD4 cell count due to immune system activation have been described after vaccination in patients with HIV in some older studies [Rey et al. 2000; Kolber et al. 2002]. The changes are less likely to occur in patients taking antiretroviral therapy (ART) and have not been found to have long-term negative effects [Sullivan et al. 2000; Rubin et al. 2014].

KEY POINTS
  • In people with HIV older than 5 years, effective ART is defined as ART taken for ≥6 months, with CD4 percentage ≥15% and CD4 count ≥200 cells/mm3 for ≥6 months [McLean et al. 2013].
  • Viral suppression is defined as HIV viral load <200 copies/mL.

Clinicians should advise their patients with HIV that their family members, close contacts, and other household members should receive all age-appropriate vaccinations, including an annual influenza vaccine, to reduce the patients’ exposure to vaccine-preventable diseases [Fiore et al. 2011; ACIP 2013; Rubin et al. 2014]. Live, attenuated virus vaccines may be safely administered to close contacts of persons with HIV, with specific precautions for varicella and rotavirus vaccines. Transmission of live, attenuated virus after vaccination is rare [Rubin et al. 2014]. However, patients with HIV who lack varicella immunity are advised to avoid direct contact with persons who develop a rash after varicella or zoster vaccination, and should not handle diapers of an infant recently vaccinated for rotavirus [Marin et al. 2007; Cortese and Parashar 2009; Fiore et al. 2011; Rubin et al. 2014].

Tables 1 through 13 (for each vaccine listed on the left) present the recommended immunizations for adults with HIV, followed by discussion of each. For complete vaccination recommendations, see CDC Immunization Schedules and the vaccine manufacturers’ package inserts.

How to File a Claim With the Vaccine Injury Compensation Program
  • Tel: 1-800-338-2382
  • Website: hrsa.gov/vaccinecompensation
  • Address to file a claim: US Court of Federal Claims, 717 Madison Place, NW, Washington DC 20005
References

Advisory Committee on Immunization Practices (ACIP). General recommendations on immunization — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64. [PMID: 21293327]

Advisory Committee on Immunization Practices (ACIP). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices–United States, 2013-2014. MMWR Recomm Rep 2013;62(Rr-07):1-43. [PMID: 24048214]

Centers for Disease Control and Prevention (CDC). Disseminated Mycobacterium bovis infection from BCG vaccination of a patient with acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1985;34(16):227-228. [PMID: 3920493]

Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep 1996;45(28):603-606. [PMID: 8676852]

Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(Rr-2):1-25. [PMID: 19194371]

Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. N Engl J Med 1977;297(5):241-245. [PMID: 195206]

Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM. Antiviral agents for the treatment and chemoprophylaxis of influenza — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(1):1-24. [PMID: 21248682]

Kolber MA, Gabr AH, De La Rosa A, Glock JA, Jayaweera D, Miller N, Dickinson GM. Genotypic analysis of plasma HIV-1 RNA after influenza vaccination of patients with previously undetectable viral loads. AIDS 2002;16(4):537-542. [PMID: 11872996]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-04):1-34. [PMID: 23760231]

Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987;316(11):673-676. [PMID: 3821799]

Rey D, Krantz V, Partisani M, Schmitt MP, Meyer P, Libbrecht E, Wendling MJ, Vetter D, Nicolle M, Kempf-Durepaire G, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine 2000;18(13):1161-1165. [PMID: 10649616]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Sullivan PS, Hanson DL, Dworkin MS, Jones JL, Ward JW. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS 2000;14(17):2781-2785. [PMID: 11125897]

Updates

June 2018

Zoster vaccine: Changes/insertions made on June 4, 2018, are indicated in red, below.

  • RZV provides strong protection against shingles and post-herpetic neuralgia. Currently, there are no data on efficacy immunogenicity specific to people with HIV; however, superior efficacy and longer duration of protection have been demonstrated among the elderly, and a recombinant vaccine is preferred people with HIV. In addition, immunogenicity and safety following a 3-dose schedule has been demonstrated among people with HIV infection [Berkowitz et al. 2015]. 
  • Note: RZV is administered IM in distinction to ZVL which is delivered by SQ injection [Shimabukuro et al. 2018] 
  • Two references added June 4, 2018:
    • Berkowitz EM, Moyle G, Stellbrink HJ, Schürmann D, Kegg S, El Idrissi M, Oostvogeis L, Heineman TC, Zoster-015 HZ/su Study Group. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomizedplacebo-controlled studyJ Infect Dis. 2015 Apr 15;211(8):1279-87. [PMID: 25371534]
    • Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: Vaccine Administration Errors Involving Recombinant Zoster Vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:585–586. [PMID: 29795075]

Haemophilus Influenzae Type B Conjugate (Hib)

Medical Care Criteria Committee, April 2018

Table 1: Hib Vaccine
Trade Names Hiberix; ActHIB
Indications  Patients at risk of Hib infection (see CDC guidelines for all adults)
Administration  Administer according to CDC guidelines for all adults at risk
Revaccination  None
Comments  Not routinely recommended for people with HIV in the absence of other risk factors (see CDC guidelines)

Discussion: Hib vaccination is not routinely recommended for patients with HIV in the absence of other risk factors, such as anatomic or functional asplenia, sickle cell disease, or hematopoietic stem cell transplant, because there is a low risk of H. influenzae type b infection in adults with HIV [Briere et al. 2014; Rubin et al. 2014; CDC 2017]. Data on the safety and efficacy of the Hib vaccine among adults with HIV indicate a strong immune response, similar to that in adults without HIV, except among those with severe immunosuppression [Steinhoff et al. 1991; Kroon et al. 1997; Dockrell et al. 1999; MacLennan et al. 2016].

References

Briere EC, Rubin L, Moro PL, Cohn A, Clark T, Messonnier N. Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2014;63(Rr-01):1-14. [PMID: 24572654]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Dockrell DH, Poland GA, Steckelberg JM, Wollan PC, Strickland SR, Pomeroy C. Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response. Vaccine 1999;17(22):2779-2785. [PMID: 10438047]

Kroon FP, van Dissel JT, Rijkers GT, Labadie J, van Furth R. Antibody response to Haemophilus influenzae type b vaccine in relation to the number of CD4+ T lymphocytes in adults infected with human immunodeficiency virus. Clin Infect Dis 1997;25(3):600-606. [PMID: 9314445]

MacLennan CA, Richter A, Hodson J, Faustini S, Birtwistle J, Whitelegg A, Chigiga J, Singo M, Walker-Haywood J, Mulugeta B, et al. Brief Report: Immunization of HIV-Infected Adults in the UK With Haemophilus influenzae b/Meningococcal C Glycoconjugate and Pneumococcal Polysaccharide Vaccines. J Acquir Immune Defic Syndr 2016;73(3):287-293. [PMID: 27163175]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Steinhoff MC, Auerbach BS, Nelson KE, Vlahov D, Becker RL, Graham NM, Schwartz DH, Lucas AH, Chaisson RE. Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection. N Engl J Med 1991;325(26):1837-1842. [PMID: 1683682]

Hepatitis A Virus (HAV)

Medical Care Criteria Committee, April 2018

Table 2: HAV Vaccine
Trade Names
  • HAV: Havrix; Vaqta
  • HAV inactivated + hepatitis B virus (HBV): Twinrix
Indications
  • Patients who: 1) are HAV IgG negative and at risk of HAV infection and related morbidity and mortality; 2) seek protection against HAV (see CDC guidelines)
  • At-risk populations, including men who have sex with men and people who:
    • Have chronic liver disease or conditions that can lead to chronic liver disease
    • Travel to countries with high or intermediate endemicity of infection
    • Use and inject illicit drugs
    • Live in a community experiencing an outbreak of HAV infection
    • Have a clotting-factor disorder
    • Are at occupational risk of HAV infection
Administration
  • Administer according to CDC guidelines
  • Obtain HAV IgG at least 1 month after final dose of vaccination series to identify nonresponders
  • If immune reconstitution appears likely, then consider deferring until patient’s CD4 count >200 cells/mm3 [AIDSinfo 2017]
Revaccination Nonresponders to primary HAV vaccination series should be revaccinated [Aberg et al. 2014] and counseled to avoid exposure
Comments

Discussion: Among patients with HIV, the HAV vaccine is recommended for those at risk of HAV infection or those who wish to reduce their risk of HAV infection [CDC 2017; WHO 2017].

The reported rate of HAV antibody seroconversion after vaccination ranges from 49% to 96% [Fiore et al. 2006; Crum-Cianflone and Wallace 2014; Mena et al. 2015]. A long-term follow-up study reported that over 85% of those who seroconverted after vaccination had a sustained antibody response for 5 to 10 years [Crum-Cianflone et al. 2011; Cheng et al. 2017]. Although immunocompetent patients with HIV respond to the HAV vaccine nearly as well as patients without HIV, patients with lower CD4 cell counts are less likely to acquire protective levels of antibody [Fiore et al. 2006; Crum-Cianflone and Wallace 2014; Mena et al. 2015].

If a patient’s CD4 count is <200 cells/mm3 or the patient has symptomatic HIV, it is preferable to defer vaccination until several months after initiation of antiretroviral therapy to maximize the antibody response to the vaccine [AIDSinfo 2017]. HAV vaccination should not be deferred in patients who are unlikely to achieve an increased CD4 cell count (see NYSDOH AI HAV-HIV Coinfection Guideline).

Care providers should perform HAV IgG at least 1 month after final dose of vaccination series to identify nonresponders. Nonresponders to HAV vaccination should be revaccinated [Aberg et al. 2014] and counseled to avoid exposure to HAV because they remain susceptible to infection, although one recent small study reported that 31% of primary nonresponders (n = 16) subsequently seroconverted after completing the two-dose vaccination series [Cheng et al. 2017]. If patients are susceptible to both HAV and HBV, the combined HAV/HBV vaccine (three doses at 0, 1, and 6 months) can be used regardless of the patient’s immune status [Aberg et al. 2014].

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Cheng A, Chang SY, Sun HY, Tsai MS, Liu WC, Su YC, Wu PY, Hung CC, Chang SC. Long-term Durability of Responses to 2 or 3 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Adults on Antiretroviral Therapy. J Infect Dis 2017;215(4):606-613. [PMID: 28011921]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

Crum-Cianflone NF, Wilkins K, Lee AW, Grosso A, Landrum ML, Weintrob A, Ganesan A, Maguire J, Klopfer S, Brandt C, et al. Long-term durability of immune responses after hepatitis A vaccination among HIV-infected adults. J Infect Dis 2011;203(12):1815-1823. [PMID: 21606540]

Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(Rr-7):1-23. [PMID: 16708058]

Mena G, Garcia-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: A review. Hum Vaccin Immunother 2015;11(11):2582-2598. [PMID: 26208678]

World Health Organization (WHO). Hepatitis A outbreaks mostly affecting men who have sex with men–European Region and the Americas. 2017 Jun 7. http://www.who.int/csr/don/07-june-2017-hepatitis-a/en/ [accessed 2018 Mar 27]

Hepatitis B Virus (HBV)

Medical Care Criteria Committee, April 2018

Table 3: HBV Vaccine
Trade names
  • HBV 2-dose series: HEPLISAV-B (see note in comments)
  • HBV 3-dose series: Engerix-B; Recombivax HB
  • Hepatitis A virus (HAV) inactivated + HBV: Twinrix
Indications Patients who are negative for anti-HBs and do not have chronic HBV infection (see CDC guidelines and the NYSDOH AI HBV-HIV Coinfection Guideline > Figure 3: Algorithm for HBV Pre-Vaccination Screening and Vaccination in Patients with HIV)
Administration
  • Administer according to CDC guidelines for all adults [Schillie et al. 2018b]
  • Alternative administration strategies, such as a 3- or 4-injection double-dose vaccination series or an accelerated schedule of 0, 1, and 3 weeks, may be considered [AIDSinfo 2017]
  • Test for anti-HBs 1 to 2 months after administration of the last dose of the vaccination series [Rubin et al. 2014]
Revaccination Nonresponders to the primary HBV vaccination series (anti-HBs <10 IU/L) should receive a double-dose revaccination series; a 4-dose schedule should be considered 
Comments
  • In patients at risk for HBV infection, initial vaccination should not be deferred if CD4 count is <200 cells/mm3 [AIDSinfo 2017]
  • If an accelerated schedule is used, a fourth dose booster should be administered at least 6 months after initiation of the series; the accelerated schedule is not recommended for patients with CD4 counts ­<500 cells/mm3
  • The HAV/HBV combined vaccine is not recommended for the double-dose or 4-injection HBV vaccination strategy
  • HEPLISAV-B, a two-dose (1 month apart) recombinant HBV surface antigen vaccine with a novel adjuvant is now available. There are no data available on use among people with HIV. There were no autoimmune adverse events among people with HIV exposed to the adjuvant [FDA 2017; Schillie et al. 2018a]
  • See NYSDOH AI HBV-HIV Coinfection Guideline
  • Covered by the Vaccine Injury Compensation Program

Discussion: The HBV vaccine is recommended for all adults with HIV who do not have immunity to HBV and who do not have chronic HBV infection [CDC 2017]. The antibody response to the HBV vaccine is reduced in persons with HIV compared with those who do not have HIV; the reported immune response to the standard dose (20 µg) ranges from 34% to 89% [Mast et al. 2006; Mena et al. 2015], with diminishing response with lower CD4 cell counts [Overton et al. 2005; Kim et al. 2008; Pettit et al. 2010; Pollack et al. 2016]. Undetectable or very low viral load is associated with increased response to HBV vaccination [Overton et al. 2005; Kim et al. 2008; Mena et al. 2012]. Initial vaccination should not be deferred in patients with low CD4 cell counts; some patients with HIV and CD4 counts <200 cells/mm3 may have an immune response [Whitaker et al. 2012; AIDSinfo 2017].

Improved immune response has been reported using a four-injection double-dose (40 µg) regimen [Launay et al. 2011; Chaiklang et al. 2013]. Studies of a three-injection double-dose regimen reported increased seroconversion rates compared to standard dose only among adults with HIV with CD4 counts >350 cells/mm3 and low or undetectable HIV viral load [Fonseca et al. 2005; Potsch et al. 2012]. Accelerated schedules (0, 1, and 3 weeks) may increase adherence to the full vaccination series but are not recommended for patients with CD4 counts ­<500 cells/mm3 due to the increased likelihood of nonresponse [de Vries-Sluijs et al. 2011]. Patients with HIV should be tested for anti-HBs 1 to 2 months after completing the vaccination series [Aberg et al. 2014; AIDSinfo 2017]. Other strategies to improve immune response have demonstrated some success, including intradermal administration [Launay et al. 2011] and addition of adjuvants [Sasaki et al. 2003; Cooper et al. 2005; Overton et al. 2010], but the evidence is not sufficient to make a recommendation.

Nonresponders to primary vaccination should be revaccinated using a double-dose regimen with consideration of a four-dose schedule. Several studies have reported increased response rates from double-dose revaccination among nonresponders [Cardell et al. 2008; de Vries-Sluijs et al. 2008; Psevdos et al. 2010], although the only randomized controlled trial comparing a three-injection standard dose (20 µg) to a three-injection, double-dose (40 µg) regimen for revaccination found no difference in response rates. However, the double-dose regimen resulted in a greater and more durable immune response [Rey et al. 2015]. HBV revaccination can be deferred among nonresponders who are initiating antiretroviral therapy until CD4 counts increase to ≥200 cells/mm3 [AIDSinfo 2017]. Revaccination should not be delayed in patients who are unlikely to achieve an increased CD4 cell count. For more detailed information, see NYSDOH AI HBV-HIV Coinfection Guideline.

Three HBV vaccination formulations are available in the United States. The efficacy of these vaccines has been reported to be equivalent when used in patients who do not have HIV; however, the three formulations have not yet been established to be equally effective in patients with HIV. For persons who are susceptible to both HAV and HBV, the combined HAV/HBV vaccine can be used regardless of immune status, with three doses, administered at 0, 1, and 6 months. Because no data are available regarding double-dose or four-injection HBV vaccination with the combined HAV/HBV vaccine in the presence of HIV, the combined vaccine is not recommended for the double-dose or four-injection HBV vaccination strategy. A two-dose (1 month apart) recombinant hepatitis B surface antigen vaccine with a novel adjuvant is available. There are no data available on use in people with HIV, but seroprotective rates were superior to comparator 3-dose series among older adults and adults with diabetes [Janssen 2017]. No autoimmune adverse events were reported among people with HIV exposed to the adjuvant [FDA 2017]. The two-dose option may facilitate completion rates for the vaccination series. For more information, see NYSDOH AI HBV-HIV Coinfection Guideline > Prevention.

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Cardell K, Akerlind B, Sallberg M, Fryden A. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. J Infect Dis 2008;198(3):299-304. [PMID: 18544037]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS One 2013;8(11):e80409. [PMID: 24265819]

Cooper CL, Davis HL, Angel JB, Morris ML, Elfer SM, Seguin I, Krieg AM, Cameron DW. CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults. AIDS 2005;19(14):1473-1479. [PMID: 16135900]

de Vries-Sluijs TE, Hansen BE, van Doornum GJ, Kauffmann RH, Leyten EM, Mudrikova T, Brinkman K, den Hollander JG, Kroon FP, Janssen HL, et al. A randomized controlled study of accelerated versus standard hepatitis B vaccination in HIV-positive patients. J Infect Dis 2011;203(7):984-991. [PMID: 21266513]

de Vries-Sluijs TE, Hansen BE, van Doornum GJ, Springeling T, Evertsz NM, de Man RA, van der Ende ME. A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients. J Infect Dis 2008;197(2):292-294. [PMID: 18177248]

Food and Drug Administration (FDA). Briefing Document. Heplisav-B (Hepatitis B Vaccine Recombinant and 1018 ISS Adjuvant). 2017 Jul 28. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM568492.pdf
[accessed 2018 Mar 27]

Fonseca MO, Pang LW, de Paula Cavalheiro N, Barone AA, Heloisa Lopes M. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Vaccine 2005;23(22):2902-2908. [PMID: 15780739]

HEPLISAV-B. Highlights of prescribing information. 2017 Nov. http://www.dynavax.com/files/7815/1026/3335/HEPLISAV-B-Package-Insert.pdf [accessed 2018 Apr 20]

Janssen R. HEPLISAV-B. Advisory Committee on Immunization Practices. 2017 Oct 25. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-10/hepatitis-02-janssen.pdf [accessed 2018 Mar 27]

Kim HN, Harrington RD, Van Rompaey SE, Kitahata MM. Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons. Int J STD AIDS 2008;19(9):600-604. [PMID: 18725550]

Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de Verdiere N, Slama L, Martin K, Lortholary O, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA 2011;305(14):1432-1440. [PMID: 21486976]

Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM, Jr., Janssen RS, Ward JW. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 2006;55(Rr-16):1-33; quiz CE31-34. [PMID: 17159833]

Mena G, Garcia-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: A review. Hum Vaccin Immunother 2015;11(11):2582-2598. [PMID: 26208678]

Mena G, Llupia A, Garcia-Basteiro AL, Diez C, Leon A, Garcia F, Bayas JM. Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice. Vaccine 2012;30(24):3703-3709. [PMID: 22446635]

Overton ET, Kang M, Peters MG, Umbleja T, Alston-Smith BL, Bastow B, Demarco-Shaw D, Koziel MJ, Mong-Kryspin L, Sprenger HL, et al. Immune response to hepatitis B vaccine in HIV-infected subjects using granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant: ACTG study 5220. Vaccine 2010;28(34):5597-5604. [PMID: 20600512]

Overton ET, Sungkanuparph S, Powderly WG, Seyfried W, Groger RK, Aberg JA. Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIV-infected persons. Clin Infect Dis 2005;41(7):1045-1048. [PMID: 16142673]

Pettit NN, DePestel DD, Malani PN, Riddell Jt. Factors associated with seroconversion after standard dose hepatitis B vaccination and high-dose revaccination among HIV-infected patients. HIV Clin Trials 2010;11(6):332-339. [PMID: 21239361]

Pollack TM, Trang le TT, Ngo L, Cuong do D, Thuy PT, Colby DJ. Response to hepatitis B vaccination among HIV-infected adults in Vietnam. J Virus Erad 2016;2(2):102-106. [PMID: 27482443]

Potsch DV, Camacho LA, Tuboi S, Villar LM, Miguel JC, Ginuino C, Silva EF, Mendonca RM, Moreira RB, Barroso PF. Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults. Vaccine 2012;30(41):5973-5977. [PMID: 22828589]

Psevdos G, Kim JH, Groce V, Sharp V. Efficacy of double-dose hepatitis B rescue vaccination in HIV-infected patients. AIDS Patient Care STDS 2010;24(7):403-407. [PMID: 20586648]

Rey D, Piroth L, Wendling MJ, Miailhes P, Michel ML, Dufour C, Haour G, Sogni P, Rohel A, Ajana F, et al. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. Lancet Infect Dis 2015;15(11):1283-1291. [PMID: 26257021]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Sasaki M, Foccacia R, de Messias-Reason IJ. Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine 2003;21(31):4545-4549. [PMID: 14575766]

Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep 2018a;67(15):455-458. [PMID: 29672472]

Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, Nelson NP. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018b;67(No. RR-1):1–31.

Whitaker JA, Rouphael NG, Edupuganti S, Lai L, Mulligan MJ. Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. Lancet Infect Dis 2012;12(12):966-976. [PMID: 23174382]

Human Papillomavirus (HPV)

Medical Care Criteria Committee, April 2018

Table 4: HPV Vaccine
Trade Names Gardasil 9
Indications All patients aged 9 to 26 years who were not previously vaccinated or did not receive a complete three-dose series (see CDC guidelines)
Administration Administer through age 26 years as a three-dose series according to CDC guidelines for adults with immunocompromising conditions
Revaccination None 
Comments
  • A two-dose schedule is not recommended [CDC 2017a]
  • Because of the broader coverage offered by the 9-valent HPV vaccine, it is the only HPV vaccine currently available in the United States (see the CDC’s HPV Vaccine Information for Clinicians for more information)
  • Although the 9-valent vaccine has not been specifically studied in people with HIV, it is expected that the response will be the same in this population as with the 4-valent vaccine
  • Follow recommendations for cervical and anal cancer screening in women with HIV and men who have received the HPV vaccine [AIDSinfo 2017]
  • Covered by the Vaccine Injury Compensation Program

Discussion: The HPV vaccine is safe and immunogenic among individuals with HIV [Giacomet et al. 2014; Kojic et al. 2014; Markowitz et al. 2014; Toft et al. 2014; Faust et al. 2016] and is recommended for females and males aged 9 to 26 years if they did not already receive a complete three-dose series [CDC 2017b]. Routine HPV vaccination is recommended for all adolescents at age 11 to 12 years [CDC 2018]. Available data do not support HPV vaccination in all adults older than 26 years, including those with HIV [Wilkin et al. 2016]. Mathematical modeling based on the quadrivalent vaccine has demonstrated that offering HPV vaccination to MSM with HIV up to age 40 years likely would be cost-effective [Lin et al. 2017]; however, this study did not account for lower vaccine response rates with increased age. Other analyses demonstrate 1) efficacy in adults older than 26 years, although at rates lower than in adolescents; 2) a comparable immune response for HPV type 16; and 3) a slightly lower immune response for HPV types 6, 11, and 18 among women aged 25 to 45 years [Munoz et al. 2009; Westra et al. 2011].

The HPV vaccine is approved by the U.S. Food and Drug Administration for preventive but not therapeutic use; there are no data to support the use of the HPV vaccine to ameliorate existing disease. In individuals who have had an abnormal Pap test result before being vaccinated, the HPV vaccine may protect against infection from HPV types other than those that caused earlier or existing cervical abnormalities. HPV vaccination should be offered regardless of CD4 cell count [AIDSinfo 2017]. Lower seroconversion rates after HPV vaccination have been reported among women with HIV who are not taking antiretroviral therapy [Kahn et al. 2013] or who have CD4 counts <200 cells/mm3 and/or HIV viral load >10,000 copies/ml, compared with women who do not have HIV [Kojic et al. 2014]. In another study, women with HIV and a suppressed viral load had a 1.74 to 3.03 times higher peak antibody response than those who did not have viral suppression at the time of first injection; the clinical significance of this finding is not known [Money et al. 2016].

In individuals who have had an abnormal Pap test before being vaccinated, the HPV vaccine may protect against infection from HPV subtypes other than those that caused earlier or existing cervical abnormalities. However, the vaccine does not cover all HPV serotypes that increase risk of cancer, and the vaccine may be less effective in individuals with HIV. In women and men with HIV who have received the HPV vaccine, clinicians should continue to follow recommendations for cervical and anal cytologic screening, including visual inspection of the anogenital area during annual examinations [AIDSinfo 2017] (see NYSDOH AI guidelines on Cervical Screening for Dysplasia and Cancer and Anal Dysplasia and Cancer).

HPV testing is not required before administration of the vaccine [Markowitz et al. 2014]. The two-dose schedule is not recommended for immunocompromised adults, including those with HIV [Meites et al. 2016]. There is no recommendation for obtaining follow-up antibody titers because the minimum protective titers have not been established and the immune response rate is high [Markowitz et al. 2014]. Although the 9-valent vaccine has not been specifically studied in people with HIV, it is the preferred vaccine because of the broader range of HPV subtypes seen in this population [AIDSinfo 2017].

References

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Clinician FAQ: CDC Recommendations for HPV Vaccine 2-Dose Schedules. 2017a Nov 30. https://www.cdc.gov/hpv/downloads/hcvg15-ptt-hpv-2dose.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017b Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger, United States, 2018. 2018 Mar 2. https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf [accessed 2018 Mar 27]

Faust H, Toft L, Sehr P, Muller M, Bonde J, Forslund O, Ostergaard L, Tolstrup M, Dillner J. Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines. Vaccine 2016;34(13):1559-1565. [PMID: 26896686]

Giacomet V, Penagini F, Trabattoni D, Vigano A, Rainone V, Bernazzani G, Bonardi CM, Clerici M, Bedogni G, Zuccotti GV. Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults. Vaccine 2014;32(43):5657-5661. [PMID: 25149430]

Kahn JA, Xu J, Kapogiannis BG, Rudy B, Gonin R, Liu N, Wilson CM, Worrell C, Squires KE. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis 2013;57(5):735-744. [PMID: 23667266]

Kojic EM, Kang M, Cespedes MS, Umbleja T, Godfrey C, Allen RT, Firnhaber C, Grinsztejn B, Palefsky JM, Webster-Cyriaque JY, et al. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis 2014;59(1):127-135. [PMID: 24723284]

Lin A, Ong KJ, Hobbelen P, King E, Mesher D, Edmunds WJ, Sonnenberg P, Gilson R, Bains I, Choi YH, et al. Impact and Cost-effectiveness of Selective Human Papillomavirus Vaccination of Men Who Have Sex With Men. Clin Infect Dis 2017;64(5):580-588. [PMID: 28011615]

Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, Bocchini JA, Jr., Unger ER. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014;63(Rr-05):1-30. [PMID: 25167164]

Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination – Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016;65(49):1405-1408. [PMID: 27977643]

Money DM, Moses E, Blitz S, Vandriel SM, Lipsky N, Walmsley SL, Loutfy M, Trottier S, Smaill F, Yudin MH, et al. HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine. Vaccine 2016;34(40):4799-4806. [PMID: 27544584]

Munoz N, Manalastas R, Jr., Pitisuttithum P, Tresukosol D, Monsonego J, Ault K, Clavel C, Luna J, Myers E, Hood S, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial. Lancet 2009;373(9679):1949-1957. [PMID: 19493565]

Toft L, Storgaard M, Muller M, Sehr P, Bonde J, Tolstrup M, Ostergaard L, Sogaard OS. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J Infect Dis 2014;209(8):1165-1173. [PMID: 24273179]

Westra TA, Rozenbaum MH, Rogoza RM, Nijman HW, Daemen T, Postma MJ, Wilschut JC. Until which age should women be vaccinated against HPV infection? Recommendation based on cost-effectiveness analyses. J Infect Dis 2011;204(3):377-384. [PMID: 21742836]

Wilkin TJ, Chen H, Cespedes M, Paczuski P, Godfrey C, Chiao E, Luque A, Webster-Cyriaque JY, Bastow B, Cranston R. ACTG A5298: A Phase 3 Trial of the Quadrivalent HPV Vaccine in Older HIV+ Adults. CROI; 2016 Feb 22-25; Boston, MA. http://www.croiconference.org/sessions/actg-a5298-phase-3-trial-quadrivalent-hpv-vaccine-older-hiv-adults

Influenza

Medical Care Criteria Committee, April 2018

Table 5: Influenza Vaccine
Trade Names See CDC flu vaccines table
Indications For all patients, as determined by CDC guidelines for all adults
Administration Administer annually during flu season (October through May) according to CDC guidelines for all adults
Revaccination None
Comments Covered by the Vaccine Injury Compensation Program

Discussion: People with HIV are at greater risk of severe morbidity from an influenza infection [Kunisaki and Janoff 2009; ACIP 2013] than people who do not have HIV and should be vaccinated annually during flu season (October through May) according to standard (CDC) guidelines for all adults [ACIP 2013; Aberg et al. 2014]. Inactivated influenza vaccine offers protective immunity in adults with HIV [Beck et al. 2012; ACIP 2013; Remschmidt et al. 2014]. Live attenuated influenza vaccine should not be used for individuals with HIV. Antibody titers lower than those observed in the general population have been reported among adults with HIV, especially among those with advanced HIV disease who are older than 35 years, have low CD4 cell counts, and have detectable viremia [Kroon et al. 2000; Yamanaka et al. 2005; Evison et al. 2009; Crum-Cianflone et al. 2011; Garg et al. 2016]. Studies comparing intradermal and intramuscular vaccines report no difference in immunogenicity, but intradermal vaccination is associated with increased likelihood of redness, swelling, and tenderness at the injection site [Garg et al. 2016; Seo et al. 2016].

The CDC does not recommend a second vaccination in individuals with HIV [ACIP 2013], although one study reported that a second dose of an adjuvanted vaccine significantly increased the rate of seroprotective responses [Bickel et al. 2011]. There is some evidence that influenza seroprotection is higher for people aged 18 years or older who are given a double-dose vaccine than for those given the standard dose vaccine, but the clinical significance of this remains unknown [Cooper et al. 2011; McKittrick et al. 2013]. Another study among children and young adults (3 to 21 years of age) found no increased immunity among participants with HIV who received the double-dose vaccine [Hakim et al. 2016]. The high-dose vaccine is not licensed for people younger than 65 years.

Results of two studies suggest a possible benefit to delaying influenza vaccination to after mid-November; patients vaccinated later in the flu season had lower rates of laboratory-confirmed influenza and influenza-like illnesses than those vaccinated earlier in the season [Werker et al. 2014; Glinka et al. 2016]. Monitoring regional influenza activity will help ensure appropriate timing of influenza vaccination. There is no recommendation for post-vaccination serologic testing to determine immune response [ACIP 2013].

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

Advisory Committee on Immunization Practices (ACIP). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices–United States, 2013-2014. MMWR Recomm Rep 2013;62(Rr-07):1-43. [PMID: 24048214]

Beck CR, McKenzie BC, Hashim AB, Harris RC, Nguyen-Van-Tam JS. Influenza vaccination for immunocompromised patients: systematic review and meta-analysis by etiology. J Infect Dis 2012;206(8):1250-1259. [PMID: 22904335]

Bickel M, von Hentig N, Wieters I, Khaykin P, Nisius G, Haberl A, Stephan C, Herrmann E, Doerr HW, Brodt HR, et al. Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients. Clin Infect Dis 2011;52(1):122-127. [PMID: 21148530]

Cooper C, Thorne A, Klein M, Conway B, Boivin G, Haase D, Shafran S, Zubyk W, Singer J, Halperin S, et al. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS One 2011;6(3):e17758. [PMID: 21512577]

Crum-Cianflone NF, Eberly LE, Duplessis C, Maguire J, Ganesan A, Faix D, Defang G, Bai Y, Iverson E, Lalani T, et al. Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in an immunocompromised population: a prospective study comparing HIV-infected adults with HIV-uninfected adults. Clin Infect Dis 2011;52(1):138-146. [PMID: 21148532]

Evison J, Farese S, Seitz M, Uehlinger DE, Furrer H, Muhlemann K. Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients. Clin Infect Dis 2009;48(10):1402-1412. [PMID: 19361304]

Garg S, Thongcharoen P, Praphasiri P, Chitwarakorn A, Sathirapanya P, Fernandez S, Rungrojcharoenkit K, Chonwattana W, Mock PA, Sukwicha W, et al. Randomized Controlled Trial to Compare Immunogenicity of Standard-Dose Intramuscular Versus Intradermal Trivalent Inactivated Influenza Vaccine in HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand. Clin Infect Dis 2016;62(3):383-391. [PMID: 26486702]

Glinka ER, Smith DM, Johns ST. Timing Matters – Influenza Vaccination to HIV-Infected Patients. HIV Med 2016;17(8):601-604. [PMID: 26810556]

Hakim H, Allison KJ, Van de Velde LA, Tang L, Sun Y, Flynn PM, McCullers JA. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection. Vaccine 2016;34(27):3141-3148. [PMID: 27129426]

Kroon FP, van Dissel JT, de Jong JC, Zwinderman K, van Furth R. Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study. Vaccine 2000;18(26):3040-3049. [PMID: 10825608]

Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 2009;9(8):493-504. [PMID: 19628174]

McKittrick N, Frank I, Jacobson JM, White CJ, Kim D, Kappes R, DiGiorgio C, Kenney T, Boyer J, Tebas P. Improved immunogenicity with high-dose seasonal influenza vaccine in HIV-infected persons: a single-center, parallel, randomized trial. Ann Intern Med 2013;158(1):19-26. [PMID: 23277897]

Remschmidt C, Wichmann O, Harder T. Influenza vaccination in HIV-infected individuals: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness and safety. Vaccine 2014;32(43):5585-5592. [PMID: 25131742]

Seo YB, Lee J, Song JY, Choi HJ, Cheong HJ, Kim WJ. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine. Hum Vaccin Immunother 2016;12(2):478-484. [PMID: 26431466]

Werker GR, Sharif B, Sun H, Cooper C, Bansback N, Anis AH. Optimal timing of influenza vaccination in patients with human immunodeficiency virus: a Markov cohort model based on serial study participant hemoagglutination inhibition titers. Vaccine 2014;32(6):677-684. [PMID: 24355089]

Yamanaka H, Teruya K, Tanaka M, Kikuchi Y, Takahashi T, Kimura S, Oka S. Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients. J Acquir Immune Defic Syndr 2005;39(2):167-173. [PMID: 15905732]

Measles, Mumps, Rubella (MMR)

Medical Care Criteria Committee, April 2018

Table 6: MMR Vaccine
Trade Names
  • M-M-R II
  • MMR + varicella: ProQuad 
Indications For patients with CD4 counts ≥200 cells/mm3 who do not have evidence of MMR immunity, as determined by CDC guidelines for all adults
Administration Two doses at least 28 days apart (see CDC guidelines)
Revaccination Recommended only in the setting of an outbreak (see CDC guidelines)
Comments
  • Contraindicated for patients with CD4 counts <200 cells/mm3 (see CDC guidelines)
  • MMR + varicella (MMRV) should not be substituted for MMR [McLean et al. 2013; Rubin et al. 2014]
  • Those who previously received two doses of a mumps-containing vaccine and are at increased risk for mumps in the setting of an outbreak should receive a third dose to improve protection against mumps disease and related complications [Marin et al. 2018]
  • Covered by the Vaccine Injury Compensation Program

Discussion: Immunocompromised persons are at increased risk of serious and life-threatening complications if infected with measles [McLean et al. 2013]. Patients with HIV who have CD4 counts >200 cells/mm3 and who do not have evidence of immunity to MMR should be vaccinated with two doses of MMR vaccine at least 28 days apart. Documentation of previous age-appropriate vaccination or laboratory confirmation of prior disease is acceptable evidence of immunity. Serologic screening is required if other acceptable evidence of immunity is not available and to determine rubella immunity among individuals of childbearing potential. In the absence of other evidence of immunity, persons with perinatally acquired HIV who received childhood vaccination with MMR before establishment of effective ART should be revaccinated (two doses) after effective antiretroviral therapy (ART) is established [McLean et al. 2013]. There is no recommendation for post-vaccination serologic testing to determine immune response [McLean et al. 2013].

Two studies that examined the antibody response after MMR vaccination in adults with HIV taking ART reported high levels of protective antibodies post-vaccination, although the levels were lower than in adults without HIV. A study conducted in Mexico among adults with HIV who were seronegative for measles reported no significant difference in initial antibody response to measles vaccination between adults with and without HIV (81% vs 85%). However, at 1 year, the observed decline in antibody response was faster in adults with HIV than in those without [Belaunzaran-Zamudio et al. 2009]. A recent study in Thailand reported protective antibodies to measles (74.1%), mumps (65.7%), and rubella (93.3%) among adults with HIV 8 to 12 weeks after vaccination with MMR. Compared with adults without HIV, the seroconversion rates were lower but reached statistical significance only for mumps [Chaiwarith et al. 2016].

No data are available on revaccination in adults with HIV. Revaccination has improved measles antibody response in children with HIV on ART who had an inadequate initial response to vaccination [Aurpibul et al. 2007; Abzug et al. 2012]. If persons previously vaccinated with two doses of a mumps-containing vaccine are identified as at increased risk for mumps by public health authorities because of an outbreak, these at-risk individuals should receive a third dose of a mumps-containing vaccine to improve protection against mumps disease and related complications [Marin et al. 2018].

MMR vaccination contains live virus and is contraindicated for patients with CD4 counts <200 cells/mm3 due to reports of adverse events, such as measles pneumonitis, in severely compromised patients [CDC 1996; Angel et al. 1998]. Serious adverse effects have not been reported in adults who were not severely immunocompromised [Belaunzaran-Zamudio et al. 2009; McLean et al. 2013; Chaiwarith et al. 2016]. MMRV has not been adequately studied in individuals with HIV and is not recommended as a substitute for MMR in this population [McLean et al. 2013; Rubin et al. 2014].

References

Abzug MJ, Qin M, Levin MJ, Fenton T, Beeler JA, Bellini WJ, Audet S, Sowers SB, Borkowsky W, Nachman SA, et al. Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy. J Infect Dis 2012;206(4):512-522. [PMID: 22693229]

Angel JB, Walpita P, Lerch RA, Sidhu MS, Masurekar M, DeLellis RA, Noble JT, Snydman DR, Udem SA. Vaccine-associated measles pneumonitis in an adult with AIDS. Ann Intern Med 1998;129(2):104-106. [PMID: 9669968]

Aurpibul L, Puthanakit T, Sirisanthana T, Sirisanthana V. Response to measles, mumps, and rubella revaccination in HIV-infected children with immune recovery after highly active antiretroviral therapy. Clin Infect Dis 2007;45(5):637-642. [PMID: 17683001]

Belaunzaran-Zamudio PF, Garcia-Leon ML, Wong-Chew RM, Villasis-Keever A, Cuellar-Rodriguez J, Mosqueda-Gomez JL, Munoz-Trejo T, Escobedo K, Santos JI, Ruiz-Palacios GM, et al. Early loss of measles antibodies after MMR vaccine among HIV-infected adults receiving HAART. Vaccine 2009;27(50):7059-7064. [PMID: 19799846]

Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep 1996;45(28):603-606. [PMID: 8676852]

Chaiwarith R, Praparattanapan J, Nuket K, Kotarathitithum W, Supparatpinyo K. Seroprevalence of antibodies to measles, mumps, and rubella, and serologic responses after vaccination among human immunodeficiency virus (HIV)-1 infected adults in Northern Thailand. BMC Infect Dis 2016;16:190. [PMID: 27138005]

Marin M, Marlow M, Moore KL, Patel M. Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak. MMWR Morb Mortal Wkly Rep 2018;67(1):33-38. [PMID: 29324728]

McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-04):1-34. [PMID: 23760231]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Meningococcal Serotype Non-B (MenACWY)

Medical Care Criteria Committee, April 2018

Table 7: MenACWY Vaccine
Trade Names
  • MenACWY: Menactra
  • MCV4: Menveo
Indications
Administration
  • Administer two doses of MenACWY at least 8 weeks apart in those not previously vaccinated (see CDC guidelines)
  • For those previously vaccinated with one dose of MenACWY, administer the second dose at the earliest opportunity at least 8 weeks after the previous dose (see CDC guidelines)
Revaccination Administer one booster dose of MenACWY every 5 years (see CDC guidelines)
Comments

Discussion: Adults with HIV are at increased risk of invasive meningococcal disease due to serogroups C, W, and Y. [MacNeil et al. 2016; Folaranmi et al. 2017]. A recent study in New York City reported a 10-fold increased risk of invasive meningococcal disease in patients with HIV, with the highest risk among those with CD4 counts <200 cells/mm3 [Miller et al. 2014]. As of 2017, the CDC recommends vaccinating all previously unvaccinated adults with HIV with a two-dose primary series of MenACWY (MenACWY-CRM or MenACWY-D) administered at least 8 weeks apart [MacNeil et al. 2016].

Data on meningococcal vaccine efficacy among adults with HIV are not currently available [MacNeil et al. 2016]. Among adolescents with HIV, available evidence indicates that the vaccine is immunogenic and serious adverse events are rare, but adolescents with HIV (and especially those with lower CD4 cell counts and higher viral loads) had reduced antibody levels compared with adolescents without HIV [Siberry et al. 2010; Lujan-Zilbermann et al. 2012]. Adding a second vaccine dose significantly improved antibody levels 28 and 72 weeks after immunization, particularly among adolescents with CD4% >15 [Lujan-Zilbermann et al. 2012].

Booster doses every 5 years are needed to maintain immunity. Although MPSV4 is the only meningococcal vaccine licensed for persons aged 56 years or older, MenACWY is preferred among older adults because of the need for revaccination. Limited data among healthy adults suggest a greater immune response after a booster dose of MenACWY than with MPSV4; however, no data are available for adults with HIV. There is no recommendation for post-vaccination serologic testing to determine immune response [MacNeil et al. 2016].

References

Folaranmi TA, Kretz CB, Kamiya H, MacNeil JR, Whaley MJ, Blain A, Antwi M, Dorsinville M, Pacilli M, Smith S, et al. Increased Risk for Meningococcal Disease among Men who have Sex with Men in the United States, 2012-2015. Clin Infect Dis 2017. [PMID: 28505234]

Lujan-Zilbermann J, Warshaw MG, Williams PL, Spector SA, Decker MD, Abzug MJ, Heckman B, Manzella A, Kabat B, Jean-Philippe P, et al. Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus. J Pediatr 2012;161(4):676-681.e672. [PMID: 22622049]

MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons – Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep 2016;65(43):1189-1194. [PMID: 27811836]

Miller L, Arakaki L, Ramautar A, Bodach S, Braunstein SL, Kennedy J, Steiner-Sichel L, Ngai S, Shepard C, Weiss D. Elevated risk for invasive meningococcal disease among persons with HIV. Ann Intern Med 2014;160(1):30-37. [PMID: 24166695]

Siberry GK, Williams PL, Lujan-Zilbermann J, Warshaw MG, Spector SA, Decker MD, Heckman BE, Demske EF, Read JS, Jean-Philippe P, et al. Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents. Pediatr Infect Dis J 2010;29(5):391-396. [PMID: 20431379]

Meningococcal Serotype B (MenB)

Medical Care Criteria Committee, April 2018

Table 8: MenB Vaccine
Trade Names Bexsero; Trumenba
Indications Patients at risk of MenB infection, as determined by CDC guidelines
Administration Administer according to CDC guidelines for patients at risk
Revaccination None
Comments

Discussion: MenB vaccine is not routinely recommended for adults with HIV unless they have another indication for immunization. No increased risk of serogroup B meningococcal disease among individuals with HIV has been reported [CDC 2017].

Reference

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Pneumococcal

Medical Care Criteria Committee, April 2018

Table 9: Pneumococcal Vaccine: 13-Valent and 23-Valent (PCV13, PPSV23)
Trade Names Prevnar 13 (PCV130); Pneumovax 23 (PPSV23)
Indications All patients with HIV (see CDC guidelines)
Administration
  • The complete series of vaccinations is one dose of PCV13 and two doses of PPSV23 before age 65 years, followed by one additional dose of PPSV23 after age 65 years (see CDC guidelines)
  • See Table 10, below, for detailed administration guidelines based on age and previous vaccination history
Revaccination See Table 10, below
Comments The PCV13 vaccine should be not be deferred for patients with CD4 count <200 cells mm3 and/or detectable viral load; however, the follow-up secondary administration of PPSV23 vaccine may be deferred until the patient’s CD4 count is >200 cells mm3 and/or viral load is undetectable 

Discussion: Individuals with HIV are at increased risk of serious disease due to Streptococcus pneumoniae, including bacteremia, meningitis, and pneumonia. Pneumococcal vaccination is recommended for all adults with HIV as soon as possible after HIV diagnosis [CDC 2012, 2017]. The complete series is one dose of PCV13 as a priming vaccine, followed by two doses of PPSV23 before age 65 years, and one additional dose of PPSV23 after age 65 years. Because only one dose of PPSV23 is recommended after a patient reaches age 65 years, those who begin vaccination at age 65 years or older should receive one dose of PCV13 and one dose of PPSV23 [Tomczyk et al. 2014]. There is no recommendation for post-vaccination serologic testing to determine immune response [CDC 2012, 2017]. See Table 10 for vaccination recommendations by previous pneumococcal immunization history and age at time of initial evaluation.

Pneumococcal vaccination has been demonstrated to reduce pneumococcal bacteremia and mortality among adults with HIV [Hung et al. 2004; Grau et al. 2005; Rodriguez-Barradas et al. 2008; Chowers et al. 2017]. Both polysaccharide and conjugate pneumococcal vaccines appear to be safe and immunogenic among adults with HIV who have CD4 counts >200 cells/mm3 [Ho et al. 2013; Bhorat et al. 2015; Rodriguez-Barradas et al. 2015; Lombardi et al. 2016]. In a recent randomized controlled trial, the prime-boost regimen of PCV13 followed by PPSV23 significantly increased antibody response compared with PPSV23 alone in adults with HIV [Sadlier et al. 2016].

Patients with CD4 counts <200 cells/mm3 are at the highest risk of pneumococcal disease. Because immunogenicity has been demonstrated for individuals with HIV with CD4 counts <200 cells/mm3 who received PCV7 [French et al. 2010], use of PCV13 may be considered in severely immunocompromised patients. Patients with HIV who have not previously received any pneumococcal vaccine should receive a dose of PCV13, regardless of CD4 cell count. Although there is evidence of the effectiveness of PPSV23 among patients with CD4 counts <200 cells/mm3, the benefit appears to be greatest among patients with viral loads <100,000 copies/mL and among those who are on antiretroviral therapy.

If zoster vaccine is also being administered, it should be separated from the pneumococcal vaccine by at least 4 weeks [Zostavax 2017].

Table 10. Pneumococcal Vaccination Recommendations for Adults with HIV, by Previous Pneumococcal Immunization History and Age at Time of Initial Evaluation (see CDC guidelines)
Previous Immunization History Aged 18-64 Years Aged 65 Years or Older

No previous PCV13/PPSV23* or unknown status

*by clinical documentation or patient self-report

  • 1 dose of PCV13, then
  • 1st dose of PPSV23 ≥8 weeks later, then
  • 2nd dose of PPSV23 ≥5 years after 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PCV13, then
  • 1 dose of PPSV23 ≥8 weeks later

No PCV13

+

1 dose of PPSV23

  • 1 dose of PCV13 ≥1 year after 1st dose of PPSV23, then
  • 2nd dose of PPSV23 if both ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PCV13 ≥1 year after 1st dose of PPSV23, then
  • 2nd dose of PPSV23 if both ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23 and 1st dose of PPSV23 was given before age 65 years

No PCV13

+

2 doses of PPSV23

  • 1 dose of PCV13 ≥1 year after most recent dose of PPSV23 and
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years after 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years and ≥8 weeks after PCV13 dose
  • 1 dose of PCV13 ≥1 year after most recent dose of PPSV23, then
  • 3rd dose of PPSV23 if ≥5 years after 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years and ≥8 weeks after PCV13 dose 

1 dose of PCV13

+

No PPSV23

  • 1st dose of PPSV23 ≥8 weeks after PCV13 dose, then
  • 2nd dose of PPSV23 ≥5 years later, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PPSV23 ≥8 weeks after PCV13 dose

1 dose of PCV13

+

1 dose of PPSV23

  • 2nd dose of PPSV23 if ≥8 weeks after PCV13 dose and ≥5 years since 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if both 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • If 1st dose of PPSV23 given before age 65 years: 2nd dose of PPSV23 ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23
  • If 1st dose of PPSV23 given at 65 years or older: No further doses of PPSV23 required

1 dose of PCV13

+

2 doses of PPSV23

  • If 2nd dose of PPSV23 given before age 65 years: 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23
  • If 2nd dose of PPSV23 given before age 65 years: 3rd dose of PPSV23 ≥8 weeks after PCV13 dose and ≥5 years since 2nd dose of PPSV23
  • If 2nd dose of PPSV23 given at 65 years or older: No 3rd dose of PPSV23 required
References

Bhorat AE, Madhi SA, Laudat F, Sundaraiyer V, Gurtman A, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in HIV-infected individuals naive to pneumococcal vaccination. AIDS 2015;29(11):1345-1354. [PMID: 25888646]

Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61(40):816-819. [PMID: 23051612]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Chowers M, Regev-Yochay G, Mor O, Cohen-Poradosu R, Riesenberg K, Zimhony O, Chemtob D, Stein M, Dagan R, Levy I. Invasive pneumococcal disease (IPD) in HIV infected patients in Israel since the introduction of pneumococcal conjugated vaccines (PCV): Analysis of a nationwide surveillance study, 2009-2014. Hum Vaccin Immunother 2017;13(1):216-219. [PMID: 27648488]

French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med 2010;362(9):812-822. [PMID: 20200385]

Grau I, Pallares R, Tubau F, Schulze MH, Llopis F, Podzamczer D, Linares J, Gudiol F. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med 2005;165(13):1533-1540. [PMID: 16009870]

Ho YL, Brandao AP, de Cunto Brandileone MC, Lopes MH. Immunogenicity and safety of pneumococcal conjugate polysaccharide and free polysaccharide vaccines alone or combined in HIV-infected adults in Brazil. Vaccine 2013;31(37):4047-4053. [PMID: 23684823]

Hung CC, Chen MY, Hsieh SM, Hsiao CF, Sheng WH, Chang SC. Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study. Vaccine 2004;22(15-16):2006-2012. [PMID: 15121313]

Lombardi F, Belmonti S, Fabbiani M, Morandi M, Rossetti B, Tordini G, Cauda R, De Luca A, Di Giambenedetto S, Montagnani F. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study. PLoS One 2016;11(6):e0156523. [PMID: 27258647]

Rodriguez-Barradas MC, Goulet J, Brown S, Goetz MB, Rimland D, Simberkoff MS, Crothers K, Justice AC. Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the Veterans Aging Cohort 5-Site Study. Clin Infect Dis 2008;46(7):1093-1100. [PMID: 18444830]

Rodriguez-Barradas MC, Serpa JA, Munjal I, Mendoza D, Rueda AM, Mushtaq M, Pirofski LA. Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial. J Infect Dis 2015;211(11):1703-1711. [PMID: 25538270]

Sadlier C, O’Dea S, Bennett K, Dunne J, Conlon N, Bergin C. Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial. Sci Rep 2016;6:32076. [PMID: 27580688]

Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, Hadler S, Pilishvili T. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged >/=65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63(37):822-825. [PMID: 25233284]

Zostavax. Package insert. 2017 Aug. https://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf [accessed 2018 Mar 27]

Tetanus, Diphtheria, and Pertussis (Tdap) and Tetanus-Diphtheria (Td)

Medical Care Criteria Committee, April 2018

Table 11: Tdap and Td Vaccines
Trade Names
  • Tdap: Adacel; Boostrix
  • Td: Tenivac; Decavac (generic 9Td)
Indications For all patients, as determined by CDC guidelines for all adults
Administration Administer according to CDC guidelines for all adults
Revaccination None
Comments Covered by the Vaccine Injury Compensation Program

Discussion: The recommendations for Tdap and Td vaccination of adults with HIV are the same as for all adults [CDC 2017]. The safety and efficacy of vaccination with Tdap has not been studied in this population [Rubin et al. 2014].

References

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Varicella

Medical Care Criteria Committee, April 2018

Table 12: Varicella Vaccine
Trade Names
  • Varicella: Varivax
  • Measles, mumps, and rubella (MMR) + varicella (MMRV): ProQuad
Indications For patients with CD4 counts ≥200 cells/mm3 who do not have evidence of immunity to varicella, as determined by CDC guidelines for all adults
Administration Administer according to CDC guidelines for all adults
Revaccination None
Comments
  • Contraindicated for patients with CD4 counts <200 cells/mm3 (see CDC guidelines)
  • Anti-varicella IgG screening should be performed in patients with no known history of chickenpox or shingles [Marin et al. 2007]
  • MMRV should not be used [Rubin et al. 2014]
  • Antiherpetic agents should be avoided at least 24 hours before and 14 days after administration [ACIP 2011]
  • An interval of at least 5 months is recommended between administration of post-exposure varicella IgG (VariZIG) and varicella vaccination [Cohn et al. 2013]
  • Clinical disease due to varicella after vaccination, a very rare event, should be treated with acyclovir [AIDSinfo 2017]
  • Covered by the Vaccine Injury Compensation Program

Discussion: Patients with HIV who have CD4 counts >200 cells/mm3 and do not have immunity to varicella should be vaccinated according to CDC guidelines for all adults with two doses of single-antigen varicella vaccine 4 to 8 weeks apart, or a second dose if they have received only one dose. Varicella vaccination contains live virus and is contraindicated for patients with CD4 counts <200 cells/mm3 because of the risk of disseminated disease [Kramer et al. 2001; Marin et al. 2007; CDC 2017]. Data on the effectiveness of varicella vaccination among adults with HIV are lacking, but vaccination has been shown to be effective among children with HIV [Marin et al. 2007; CDC 2012; Crum-Cianflone and Wallace 2014].

Clinicians should verify varicella immunity due to the possibility of severe disease in individuals with HIV. Birth before 1980 is not accepted as evidence of immunity in immunocompromised persons; anti-varicella IgG screening should be performed in patients with HIV who have no known history of chickenpox or shingles [Marin et al. 2007]. Post-vaccination serologic testing to determine immune response is not recommended because commercially available assays lack sensitivity and may give false-negative results [Marin et al. 2007]. Clinical disease due to varicella after vaccination, a very rare event, should be treated with acyclovir [Marin et al. 2007; AIDSinfo 2017]. If household members or close contacts develop a rash after vaccination, individuals with HIV should avoid contact with the affected person until after the rash resolves [Marin et al. 2007; ACIP 2011; Rubin et al. 2014]. Because they can interfere with vaccine virus replication and decrease vaccine effectiveness, all antiherpetic agents should be avoided for at least 72 hours before varicella vaccination through 14 days after [CDC 2016]. If post-exposure varicella immune globulin is given, clinicians should wait at least 5 months before vaccination [ACIP 2011].

References

Advisory Committee on Immunization Practices (ACIP). General recommendations on immunization — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64. [PMID: 21293327]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep 2012;61(12):212. [PMID: 22456121]

Centers for Disease Control and Prevention (CDC). Varicella. Epidemiology and Prevention of Vaccine-Preventable Diseases. 2016 Dec 30. https://www.cdc.gov/vaccines/pubs/pinkbook/index.html [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, Baker CJ, Messonnier NE. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-2):1-28. [PMID: 23515099]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

Kramer JM, LaRussa P, Tsai WC, Carney P, Leber SM, Gahagan S, Steinberg S, Blackwood RA. Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Pediatrics 2001;108(2):E39. [PMID: 11483849]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Zoster

Medical Care Criteria Committee, April 2018

Table 13: Zoster Vaccine
Trade Names Shingrix: Recombinant zoster vaccine (RZV), adjuvanted—PREFERRED
Indications Medical Care Criteria Committee recommendation: Patients with HIV ≥50 years of age (A2)
Administration
  • Two IM doses, spaced 2 to 6 months apart, regardless of past receipt of zoster live vaccine (ZVL)
  • RZV is preferred over the ZVL [Dooling et al. 2018] (AII)
  • Perform anti-varicella IgG screening in patients with no known history of chickenpox or shingles
Comments
  • RZV provides strong protection against shingles and post-herpetic neuralgia. Currently, there are no data on immunogenicity specific to people with HIV; however, superior efficacy and longer duration of protection have been demonstrated among the elderly, and a recombinant vaccine is preferred people with HIV. In addition, immunogenicity and safety following a 3-dose schedule has been demonstrated among people with HIV infection [Berkowitz et al. 2015].
  • Note: RZV is administered IM in distinction to ZVL which is delivered by SQ injection [Shimabukuro et al. 2018].
  • ZVL (brand name Zostavax) is also available, but is not recommended for people with HIV, and is contraindicated in patients with CD4 count <200 cells/mm3 (see CDC guidelines).
  • If RZV is not available and ZVL must be administered:
    • Perform anti-varicella IgG screening in patients with no known history of chickenpox or shingles
    • Instruct patients to avoid antiherpetic agents for 1 to 2 days before vaccination through 14 days after [Marin et al. 2007]
    • Separate administration of ZVL from administration of pneumococcal vaccine by at least 4 weeks [Zostavax 2017]

Discussion: Patients with HIV are at increased risk of zoster (initial episodes and recurrences) at all stages of HIV disease; the risk is greater among those with severe immunodeficiency and lower CD4 cell counts [Harpaz et al. 2008; Blank et al. 2012]. Zoster vaccination may reduce disease burden in individuals with HIV; however, data on the use of zoster vaccine among adults with HIV are limited.

The Advisory Committee on Immunization Practices recommends the RZV for use in immunocompetent adults aged ≥50 years. As noted above, this Committee recommends two doses of RZV, administered 2 to 6 months apart, for adults with HIV ≥50 years of age. RZV provides strong protection against shingles and post-herpetic neuralgia. There is no specific data on immunogenicity in people with HIV, however superior efficacy and longer duration of seroprotection have been demonstrated in the elderly, and a recombinant vaccine is preferred over a live attenuated vaccine in this population [Dooling et al. 2018].

Limited data are available on the immunogenicity of live attenuated zoster vaccine in people with HIV (ZVL). The Committee does not recommend use of ZVL in people with HIV due to the potential for adverse effects and for interference by co-administered antiviral and immune globulin therapy [Benson et al. 2012; Shafran 2016]. If ZVL is used due to lack of access to RZV, CDC guidelines recommend that, if possible, antiherpetic agents should be avoided 1 to 2 days before through 14 days after administration of the zoster vaccine [Harpaz et al. 2008]. In addition, zoster vaccine should be separated from pneumococcal vaccine by at least 4 weeks [Zostavax 2017]. Anti-varicella IgG screening should be performed in patients with no known history of chickenpox or shingles. Zoster vaccination is contraindicated for patients with CD4 counts <200 cells/mm3 [Harpaz et al. 2008]. There is no recommendation for post-vaccination serologic testing to determine immune response [Harpaz et al. 2008].

References

Benson CA, Hua L, W. AJ, Jiang JH, Bozzolo DR, Bergstrom K, Annunziato PW, Read SW, Pollard R, Rusin D, et al. Zostavax is generally safe and immunogenic in HIV-infected adults with CD4 counts ≥200 cells/μL virologically suppressed on ART: Results of a Phase 2, randomized, placebo-controlled trial. Oral abstract 96. CROI; 2012 Mar 5-8; Seattle, WA. http://www.viraled.com/modules/info/files/files_4f68abf5b1ba1.pdf

Berkowitz EM, Moyle G, Stellbrink HJ, Schürmann D, Kegg S, El Idrissi M, Oostvogeis L, Heineman TC, Zoster-015 HZ/su Study Group. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomizedplacebo-controlled studyJ Infect Dis. 2015 Apr 15;211(8):1279-87. [PMID: 25371534]

Blank LJ, Polydefkis MJ, Moore RD, Gebo KA. Herpes zoster among persons living with HIV in the current antiretroviral therapy era. J Acquir Immune Defic Syndr 2012;61(2):203-207. [PMID: 22766968]

Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, Harpaz R. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67(3):103-108. [PMID: 29370152]

Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57(Rr-5):1-30; quiz CE32-34. [PMID: 18528318]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

Shafran SD. Live attenuated herpes zoster vaccine for HIV-infected adults. HIV Med 2016;17(4):305-310. [PMID: 26315285]

Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: Vaccine Administration Errors Involving Recombinant Zoster Vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:585–586. [PMID: 29795075]

Zostavax. Package insert. 2017 Aug. https://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf [accessed 2018 Mar 27]

Summary of Recommended Vaccines for Adults with HIV

Medical Care Criteria Committee, April 2018

Click here to download full PDF version of the below table

Coordination of Care and Services

Medical Care Criteria Committee, March 2007

RECOMMENDATIONS
Initial Visit (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 (March 2007)
  • 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 (March 2007)
  • 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 (March 2007)
  • 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)

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

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

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, update dates listed below

ALL RECOMMENDATIONS: PRIMARY CARE APPROACH GUIDELINE
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. (III)
  • Clinicians should involve patients in decisions regarding HIV treatment. (III)
HIV-Related History (November 2014)
  • Clinicians should obtain a baseline and an ongoing HIV-related history according to Table 1. (A1)
  • When obtaining an HIV-related history, clinicians should:
    • Use vocabulary that patients can understand, regardless of educational level (A3)
    • Assess patients’ health literacy* (A3)
    • 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 (A3)
  • Clinicians should stress the confidential nature of discussions regarding sexual history, mental health, and substance use. (A3)
  • 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.
Mental Health and Substance Use Assessment (November 2014)
  • All HIV-infected patients should receive baseline and ongoing assessment for the following: (A1)
    • 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. (A3)
  • Clinicians should refer patients to appropriate mental health and substance use treatment providers when indicated. (A2)

*As defined by the National Network of Libraries of Medicine, 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 through the National Network of Libraries of Medicine. Professional development and training for adult education is available through the Literacy Assistance Center.

Baseline and Annual 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.
General Appearance, Vital Signs, and Weight (November 2014)
  • 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).
Pain (November 2014)
  • 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.
Ophthalmologic Assessment and Referral (November 2014)
  • Patients with CD4 counts <50 cells/mm3 should be examined by an ophthalmologist at baseline and every 6 months. (A3)
  • Patients with visual disturbances or unremitting ocular symptoms, regardless of CD4 cell count, should be evaluated by an ophthalmologist. (A3)
  • 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).
Head, Ears, Nose, Mouth, Throat, and Neck (November 2014)
  • 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 (A3)
    • Edentulous patients for intraoral examinations annually, including assessment for denture fit and screening for mucosal lesions including oral cancer (A3)
  • 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.
Genitourinary (November 2014)
  • 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. (A3)
Neuropsychological Examination (November 2014)
  • 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.
Routine Lab Testing (March 2011)
  • Clinicians should order appropriate laboratory assessments and screening tests for managing the care of patients with HIV (see Table 3. Routine Laboratory Testing and Diagnostic Screening). (III)
Virologic Assessment (March 2011)
  • 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)
Immunologic Assessment (March 2011)
  • The CD4 lymphocyte profile should include both the absolute count and percentage. (I)
TB Evaluation (March 2011)
  • 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)
Laboratory Screening for STIs (March 2011)
  • 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).
Cytological Screening (March 2011)
  • 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.
Anal Pap Tests (March 2011)
  • 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)
Risk Reduction (March 2007)
  • Clinicians should provide routine HIV risk-reduction counseling and behavioral health counseling for HIV-infected patients. (I)
Education on Safer Sex (March 2007)
  • 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)
Substance Use Counseling (March 2007)
  • 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)
Tobacco Use Assessment and Counseling (March 2007)
  • 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.
Reproductive Counseling (March 2007)
  • Clinicians should discuss family planning with patients, including risks to the mother and fetus during pregnancy.
Domestic Violence (March 2007)
  • 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.
Psychosocial Assessment (March 2007)
  • 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)
Standard Health Maintenance (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)
Opportunistic Infection Prophylaxis (March 2011)
  • Clinicians should initiate prophylaxis for specific opportunistic infections as indicated in Table 4 and discontinue it as indicated in Table 5. (I)
Immunizations for Adults with HIV (April 2018)

See full Summary of Recommended Vaccines for Adults with HIV

Initial Visit (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 (March 2007)
  • 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 (March 2007)
  • 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 (March 2007)
  • 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)