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Ward 86 Management Recommendations

Ward 86 Approach to Preventive Management for HIV Patients

updated September 2017

Contributors: Elizabeth Imbert, MD
Paula Lum, MD
Annie Luetkemeyer, MD
Mark A. Jacobson, MD

While effective antiretroviral therapy (ART) can prevent nearly all the mortality and morbidity caused by AIDS-defining opportunistic infections and malignancies, HIV-infected patients with undetectable viral loads on ART continue to experience higher rates of cardiovascular, kidney, liver, and bone disease, in addition to an increased incidence of certain non-AIDS-defining malignancies and invasive pneumococcal infections, compared with the general population. This greater risk of "non-AIDS" complications appears to be caused by the systemic inflammatory state and T-cell activation that often persists despite effecctive ART. Incomplete immune reconstitution, concomitant substance use disorder (in particular, tobacco and amphetamine use), and adverse effects of antiretroviral drugs may also have a role in increasing risk of these "non-AIDS" complications. However, the risk of many of these complications can be reduced by rigorous screening, vaccination, appropriate prophylaxis, and behavioral interventions. Although preventive management in HIV-infected patients is complex, it can greatly benefit this population.(1)

This topic is our perspective on:

Monitoring of absolute CD4 T-cell count and HIV viral load

Repeat CD4 cell count monitoring is of essentially no clinical utility for adherent patients who have demonstrated undetectable HIV viral loads on ART for at least 1 year and whose absolute CD4 count has consistently been >200 cells/µL. Even long-term virologically suppressed patients whose absolute CD4 count is in the 100-200 cells/µL range appear to be at minimal risk of opportunistic infections. On the other hand, we have observed patients with sustained virologic suppression on ART and absolute CD4 counts plateauing at <100 cells/µL develop opportunistic infections. Therefore, for patients whose CD4 cell counts are this low despite suppressed HIV RNA, checking the CD4 count every 6 months may impact clinical management decisions (eg, when to institute and discontinue prophylaxis for Mycobacterium avium complex).

For ART-adherent patients who have had an undetectable HIV viral load on ART for at least 1 year and whose absolute CD4 count is >200 cells/µL, we do continue to monitor HIV viral loads at 6-month intervals to confirm ongoing virologic suppression.

Opportunistic infection screening and prophylaxis

  • Pneumocystis pneumonia: Patients with an absolute CD4 count of <200 cells/µL should receive prophylaxis for Pneumocystis pneumonia. The need for prophylaxis in patients who have durable virologic suppression on ART and a CD4 count that has plateaued in the 100-200 cells/µL range is questionable. See Prophylaxis section of Pneumocystis topic for regimen details.
  • Toxoplasmosis: We obtain a serum Toxoplasma gondii IgG for all patients who enter care with an absolute CD4 count of <200 cells/µL (or higher CD4 counts if they decline to initiate ART). Patients who have an absolute CD4 count of <100 cells/µL and a positive Toxoplasma gondii IgG titer should receive prophylaxis for toxoplasmosis. See Prophylaxis section of Pneumocystis topic for details on Toxoplasma prophylaxis.
  • Disseminated M avium complex: Patients with an absolute CD4 count of <50 cells/µL should receive prophylaxis for M avium complex, See section 8 of Diagnosis and Management of Disseminated Mycobacterium avium Complex Infection topic for regimen details.
  • Tuberculosis (TB): We recommend yearly screening of all HIV-infected patients not already known to have latent tuberculous infection by skin testing or a blood interferon-gamma release assay (IGRA). See TB (Diagnosis) topic for details. All patients with positive test results should be ruled out for active TB and treated for latent tuberculous infection (LTBI), unless they have already been treated. See TB (Treatment) topic, Table 1, for recommended regimens.

Vaccinations

  • Hepatitis A: All patients who test seronegative for hepatitis A total antibodies should receive the standard prime/boost regimen of hepatitis A vaccine. Of note, in 2016-17, an unusual increase in cases of hepatitis A affecting men who have sex with men (MSM), people with substance use disorder, and homeless people was reported by low-endemicity countries, including the United States.
  • Hepatitis B: All patients who test seronegative for hepatitis B surface antigen, antihepatitis B surface antibody, and antihepatitis B core antibody should receive the standard prime/boost regimen of hepatitis B vaccine. (Of note, in our clinic, we give HIV-infected patients the "double dose" of hepatitis B vaccine; ie, the 40 mcg dose for the prime and booster shots.) For patients with isolated hepatitis B core antibody (ie, surface antigen and antibody negative), we recommend HBV DNA testing to determine whether occult active HBV infection is present. Those who test HBV DNA negative should be vaccinated as above; those who test positive for HBV DNA should receive a tenofovir-based ART regimen and have surveillance by liver ultrasound (even after HBV DNA becomes undetectable) to screen for early hepatocellular carcinoma (HCC) as described below under Cancer screening.
  • Human papillomavirus (HPV): HPV vaccination is recommended for HIV-infected males and females 13-26 years of age as primary prevention for anal and cervical cancer, which both have an increased incidence in HIV-infected people, even for those individuals whose HIV viral load is suppressed.
  • Streptococcus pneumoniae: All patients should receive the prime/boost regimen of 13-valent pneumococcal vaccine followed 2-6 months later by the 23-valent vaccine. (See Community-Acquired Pneumonia topic for more details.)
  • Influenza: All patients should receive influenza vaccine, preferably the injectable inactivated form, yearly.
  • Tetanus/diphtheria/pertussis (Tdap): Tdap vaccine should be administered once every 10 years. Tetanus/diphtheria is a reasonable alternative for subsequent vaccines after initial vaccination with Tdap.
  • Meningococcal disease: Clusters of serogroup C meningococcal disease among MSM have been reported in recent years. In May 2017, the CDC published results of an analysis of all 527 cases of confirmed meningococcal disease known to have occurred in the United States between January 2012 and June 2015.(2) The relative risk for MSM was 4-fold higher than for non-MSM, and among MSM the relative risk was 10-fold higher for those who were HIV infected. We now offer routine vaccination with the quadrivalent meningococcal conjugate vaccine to all HIV-infected MSM patients.
  • Varicella/zoster: Patients with no history of chickenpox or zoster should be tested for varicella-zoster virus (VZV) IgG. Those with a negative result should receive live attenuated varicella vaccine once their HIV viral load has been suppressed.
    We consider the herpes zoster (shingles) vaccine in patients who are ≥60 years of age who have a CD4 count of ≥200 cells/µL with virologic suppression on ART and a positive VZV IgG titer or a history of chickenpox.
  • Other necessary live attenuated vaccines (eg, measles, mumps, and rubella [MMR], polio) should be deferred until the patient has an undetectable HIV viral load and the CD4 count is >200 cells/µL.

Surveillance for sexually transmitted diseases (STDs)

We regularly obtain a history of recent sexual activity and screen all patients for STDs according to their possible risks and sites of exposure.

For asymptomatic MSM who have condomless oral or insertive and/or receptive anal intercourse with men, we test for gonorrhea and chlamydia at all sites of possible exposure (throat and rectal swabs, and first-catch urine for urethral testing) using nucleic acid amplification testing (NAAT) at least every 6 months. For asymptomatic MSM who have any mode of condomless sex, we obtain a serum rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test at least every 6 months. We always obtain test specimens at the sites of contact if an MSM is symptomatic or tells us he has had a high-risk exposure. We treat empirically for a particular STD if a patient's partner has informed the patient he has been diagnosed with it.

We regularly screen women as needed if they have risk factors for gonorrhea, chlamydia, or syphilis. We also screen women annually for trichomonas with a NAAT of a vaginal swab or urine specimen, with treatment for both the patient and her partner if indicated.

Cancer screening

Certain malignancies occur at higher rates in HIV-infected persons than in uninfected persons. Based on recent data from the United States,(3) anal cancer occurs 38 times more frequently in HIV-infected people. Cervical cancer occurs 3 times more frequently, liver cancer occurs 3 times more frequently, and lung cancer twice as frequently among HIV-infected people.

  1. Anal cancer
    We recommend performing an anal Papanicolaou (Pap) test and digital anal examination upon initiation of care for both women and men who have sex with men. If the result is normal, we repeat the Pap and digital exam of the anus yearly. We refer patients with an abnormal digital exam result or a Pap revealing low-grade squamous intraepithelial lesions (LSIL) or more advanced premalignant (eg, ASCUS-H, high-grade intraepithelial lesions [HSIL]) or malignant cells for high-resolution anoscopy (HRA) and biopsy of suspicious lesions. Some us also refer patients whose Pap reveals atypical squamous cells of undetermined significance (ASCUS) for HRA.
  2. Cervical cancer
    Women <30 years of age: A Pap test should be performed within 1 year of onset of sexual activity regardless of the mode of HIV transmission but no later than age 21. HIV-infected women 21 to 29 years of age should have a Pap test at the time of initial diagnosis with HIV. Provided the initial Pap result is normal, the next Pap test should be in 12 months. Some experts recommend a Pap test at 6 months after baseline. If the results of 3 consecutive Pap tests are normal, follow-up Pap testing should be performed every 3 years. Pap and HPV cotesting is not recommended. If a Pap test reveals ASCUS and a reflex HPV test result is positive, referral for colposcopy is recommended. If HPV testing is not available, cytology should be repeated in 6-12 months. For any cytology result equal to or greater than ASCUS on repeat cytology, referral to colposcopy is recommended. For LSIL or more serious (including ASC-H, atypical glandular cells [AGC], and HSIL), referral to colposcopy is recommended regardless of the results of HPV testing, if done.
    Women >30 years of age: Cervical cancer screening in HIV-infected women should continue throughout a woman's lifetime. Either Pap testing only or Pap and HPV cotesting is acceptable for screening. Recommendations for Pap testing are the same as those for women <30 years of age. If HPV cotesting is available, it can be done at the time of diagnosis or age 30, and cotest-negative women can wait to have their next cervical cancer screening in 3 years. Those who are Pap-test normal but positive for HPV should have repeat cotesting in 1 year (unless genotype test results for HPV16 or HPV16/18 are positive) and if either of the cotest results is abnormal at 1 year, referral for colposcopy is recommended. However, if the initial HPV results identify HPV16 or HPV16/18, then referral to colposcopy is recommended at that point. Recommendations for next steps based on Pap results follow recommendations for women below age 30.
  3. Liver cancer
    Most liver malignancies in HIV-infected patients are HCC resulting from chronic hepatitis C (HCV) or B (HBV) infection or chronic alcohol abuse. All these underlying conditions are more prevalent among HIV-infected patients than in the general population. Prevention of HCC (as well as end-stage liver disease) can best be achieved by:
    1. Early diagnosis and treatment of HCV infection. We routinely perform a serum HCV antibody test yearly in patients not known to have HCV infection who inject drugs or have unprotected sex.
    2. Appropriate HBV vaccination (see Vaccinations, above).
    3. Treatment of HBV for patients known to be hepatitis B surface antigen positive or HBV DNA positive in blood. We typically use combined tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) plus emtricitabine or lamivudine as part of the ART regimen to cotreat HBV and HIV; if TDF and TAF are contraindicated, we will add another medication for the HBV (eg, entecavir).
    4. Screening and treatment for unhealthy alcohol use.
    5. Evaluation of unexplained transaminitis: In patients who have either chronic HCV or HBV, we will check for occult infection by the other hepatitis virus with an HCV RNA or HBV DNA assay. Occult HCV and HBV infection each have been reported to occur in up to 10% of HIV patients who have transaminitis but are HCV antibody negative or HBV core antibody positive/HBV surface antigen and surface antibody negative.
    6. All patients with chronic HBV infection (ie, serum HBsAg positive), even if HBV is undetectable on current antiviral therapy, should be screened for HCC with ultrasound (with or without an accompanying serum alpha-fetoprotein test) every 6 months according to the age- and race-based guidelines provided by the American Association for the Study of Liver Disease (AASLD).(4) Of note, these guidelines do not provide recommendations specifically for Caucasian patients, for whom many experts recommend screening according to the guidelines for Asians. It is not known whether all HIV-infected patients with chronic HBV should be screened for HCC beyond the recommendations set forth in the AASLD guidelines; however, given the increased risk of liver fibrosis, HCC incidence, and aggressive HCC, it is reasonable to offer HCC screening to all HIV-infected patients with active HBV, recognizing that there are no data to support this recommendation.
    7. All individuals with cirrhosis should be screened for HCC every 6 months, including those with current HCV infection as well as those who have been cured of HCV infection, as the risk of HCC decreases with HCV cure but does not return to baseline in those with known cirrhotic disease, even if the fibrosis has improved.
  4. Lung cancer
    1. Tobacco cessation is essential for prevention of lung cancer and other smoking-related diseases. Effective medical interventions (ideally combined with some form of cessation counseling) include:
      1. Daily nicotine replacement patches for patients who smoke >10 cigarettes per day with a tapering regimen of 21 mg/day for 6 weeks, then 14 mg/day for 2 weeks, then 7 mg/day for 2 weeks.
      2. Bupropion SR 150 mg/day for 3 days, then 150 mg BID for 7-12 weeks. This regimen should be initiated 1-2 weeks before the quit date.
      3. Varenicline 0.5 mg daily for 3 days, then 0.5 mg BID for 4 days, then 1 mg BID for 12-24 weeks. The dosage should be reduced in patients whose estimated creatinine clearance is <30 mL/min. Of note, varenicline appears to be more effective as a single agent than nicotine replacement or bupropion. These interventions may be combined (ie, varenicline plus bupropion; nicotine replacement patch plus a lozenge or gum).
    2. The U.S. Preventive Services Task Force has given a Grade B recommendation to annual screening with a low-dose helical chest CT scan for patients 55-80 years of age who have a >30 pack-year smoking history. We consider such screening appropriate.
  5. Colon and breast cancer
    Although these solid tumors have not been reported to be more frequent in HIV-infected than in HIV-uninfected patients, there is emerging evidence suggesting these two cancers may occur at younger ages and may be more aggressive in the HIV-infected population. Thus, standard-of-care surveillance is important.
    1. Yearly stool occult blood or fecal immunochemical testing, or colonoscopy at 10-year intervals, for all adults over 50 years of age.
    2. Biennial screening mammography for women 50-74 years of age.

Preventing cardiovascular disease

Because of the well-documented increased incidence of myocardial infarction and stroke among HIV-infected patients on ART compared with matched HIV-negative controls in cohort studies, we recommend every 6- to 12-month monitoring of blood pressure, fasting lipids, and blood glucose (fasting glucose or hemoglobin A1c), as well as tobacco cessation intervention for smokers (see Lung cancer, above). We recommend diet changes, weight loss, and exercise as appropriate. See the Management of Hyperlipidemia in HIV-Infected Patients topic for specific recommendations.

Preventing chronic kidney disease

Kidney disease occurs with increased frequency in HIV-infected people and is associated with increased morbidity and mortality. We recommend checking serum creatinine/GFR and urine protein for patients upon entry into care and every 6 (creatinine/GFR) or 12 months (urine protein), with an increased frequency of monitoring for those who have hypertension or chronic HCV infection, or receive TDF in their ART regimens. We avoid TDF in patients with a GFR of <60 mL/min and stop TDF in patients who experience a GFR decline of >25% or a drop to <60 mL/min. Many of us now substitute TAF, which has a lower risk of nephrotoxicity, for TDF in all patients.

Preventing osteoporosis

See Osteoporosis topic for specific management recommendations.

Approaching medication adherence and improving retention in care

See Adherence and Retention topic.

Addressing unhealthy substance use

Unhealthy substance use can hasten disease progression, affect adherence to ART, and worsen overall consequences of HIV.(5) We endorse a harm reduction approach to substance use disorders and the use of nonjudgmental language that respects the worth and dignity of all persons and avoids perpetuating stigma.(6,7) Harm reduction is a public health philosophy that promotes methods of reducing the physicall, social, emotional, and economic harms associated with drug and alcohol use and other harmful behaviors that impact individuals and their communities. Harm reduction methods are free of judgment and directly involve clients in setting their own health goals, which often focus initially on incremental reductions in substance use and unsafe practices. Relapse or periods of return to unsafe health practices are not conceptualized as "failure of treatment." Specific approaches to substance use disorder treatment in HIV-infected patients are discussed below in Table 1.

Table 1. Approaches to the Identification and Treatment of Unhealthy Substance Use

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an approach applicable to any substance use problem.

  • This involves asking permission to discuss alcohol and drugs and normalizing this discussion. For alcohol use, we recommend a prescreen question: "Do you sometimes drink beer, wine, or other alcoholic beverages?" followed by a screen: "How many times in the past year have you had 5 (for men, 4 for women) or more standard drinks in a day?" For drug use, we recommend asking the validated single-question screener, "How many times in the past year have you used an illegal drug or a prescription medication for nonmedical reasons?"
  • If the patient answers anything greater than 0 for the alcohol screen or drug use question, proceed with an assessment of the quantity and pattern of use, and assess for substance use disorder (SUD) and other consequences. The Alcohol Use Disorders Identification Test (see AUDIT) is a 10-item tool developed by the World Health Organization that can be administered to assess alcohol consumption, drinking behaviors, and alcohol-related problems.
  • Summarize for the patient your assessment of substance use, and explain its complications and consequences.
  • Ask permission to share information about health effects of drinking/drug use.
  • Provide feedback using the "elicit, provide, elicit" model.
  • Assess the degree of readiness. If low, enhance motivation using open-ended questions, affirmations, reflections, and summaries. If high, proceed to action planning. If above-safe drinking limits or illicit drug use with consequences or mild SUD, provide brief intervention during the office visit. If moderate to severe SUD, provide medical management with evidence-based addiction pharmacotherapies, behavioral therapies, or referral to treatment (ie, medically supervised withdrawal, intensive outpatient or residential treatment).

Treatments for Substance Use Disorders

Alcohol use disorder

  • We recommend offering a full range of treatments including medications, counseling, mutual support groups (eg, 12-step, SMART Recovery, LifeRing Secular Recovery, Women for Sobriety), medically supervised withdrawal, and relapse prevention. Naltrexone, which blocks opioid receptors that are involved in the rewarding effects of drinking alcohol and the craving for alcohol, can reduce relapses to heavy drinking. A minimum initial period of 3 months of pharmacotherapy is recommended, although an optimal treatment duration has not been established. In one study, HIV viral load decreased from pre- to postnaltrexone prescription.(8) Pharmacotherapy for alcohol use disorder is most effective when combined with some behavioral support that promotes recovery. (See Helping Patients Who Drink Too Much & Medication for the Treatment of Alcohol Use Disorder) for more information.)

Opioid use disorder

  • Preventing the needle-related complications of opioid use disorder includes access to sterile needles, safe storage and disposal of sharps, and safer injection techniques and safe consumption spaces.
  • FDA-approved pharmacotherapies for the treatment of opioid use disorder include: methadone, buprenorphine, and extended-release naltrexone. Office-based treatment with buprenorphine in HIV patients has been associated with increased ARV use, improved quality of life, and decreased opioid use.(9) Methadone maintenance treatment in HIV patients has been associated with virologic suppression and CD4 count increase.(10) Patients for whom currently approved pharmacotherapies have failed may be candidates for heroin-assisted treatment, which is not available in the United States but has been shown to be effective in Europe and Canada.(11)
  • Providers should prescribe naloxone to patients with opioid use disorder as an available emergency treatment to counter the effects of opioid overdose.

Methamphetamine use disorder

  • For more information on management of HIV-infected patients who use methamphetamine, see Methamphetamine topic.

References

  1. Aberg JA, Gallant JE, Ghanem KG, et al; Infectious Diseases Society of America. 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 Jan;58(1):1-10.
  2. Folaranmi TA, Kretz CB, Kamiya H, et al. Increased risk for meningococcal disease among men who have sex with men in the United States, 2012-2015. Clin Infect Dis. 2017 May 13. [Epub ahead of print]
  3. Robbins HA, Pfeiffer RM, Shiels MS, et al. Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst. 2015 Feb 6;107(4).
  4. Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.
  5. Centers for Disease Control and Prevention. HIV and Substance Use in the United States. October 25, 2016.
  6. Broyles LM, Binswanger IA, Jenkins JA, et al. Confronting inadvertent stigma and pejorative language in addiction scholarship: a recognition and response. Subst Abus. 2014;35(3):217-21.
  7. Kelly JF, Wakeman SE, Saitz R. Stop talking 'dirty': clinicians, language, and quality of care for the leading cause of preventable death in the United States. Am J Med. 2015 Jan;128(1):8-9.
  8. Tetrault JM, Tate JP, McGinnis KA, et al; Veterans Aging Cohort Study Team. Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone. Alcohol Clin Exp Res. 2012 Feb;36(2):318-24.
  9. Korthuis PT, Fiellin DA, Fu R, et al; BHIVES Collaborative. Improving adherence to HIV quality of care indicators in persons with opioid dependence: the role of buprenorphine. J Acquir Immune Defic Syndr. 2011 Mar;56 Suppl 1:S83-90.
  10. Palepu A, Tyndall MW, Joy R, et al. Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy. Drug Alcohol Depend. 2006 Sep 15;84:188-94.
  11. Oviedo-Joekes E, Brissette S, Marsh DC, et al. Diacetylmorphine versus methadone for the treatment of opioid addiction.N Engl J Med. 2009 Aug 20;361(8):777-86.