03. Primary Care for HIV-infected Adults

Resident Editor: Ashley M. McMullen, MD

Faculty Editor: Brent Kobashi, MD

BOTTOM LINE

✔ A detailed history of a patient’s HIV history, social history, and symptom review is important.

✔ Patients on ART require regular lab monitoring.

✔ Those living with HIV are at increased risk of non-AIDS related illnesses, including CV disease, malignancy, renal & liver disease.

Background

  • Patients with HIV on ART (anti-retroviral therapy) can live long lives and need primary care beyond HIV care.
  • Initial evaluation includes reviewing history of HIV, risk behaviors, history of opportunistic infections and laboratory testing.
  • Patients with HIV on ART can experience medication side effects that need monitoring including dyslipidemia, glucose intolerance, hepatotoxicity, and nephrotoxicity.

Initial Evaluation of HIV Infection

  • Confirm diagnosis with documentation of prior testing or repeat testing if documentation unavailable.
    • Screening is typically done with a fourth-generation combination HIV antigen/antibody test to detect both HIV antibody and HIV p24 antigen
    • A positive screening test must be confirmed using the HIV-1/HIV-2 differentiation assay (preferred) or Western blot 
  • Review the patient’s understanding of HIV and HIV transmission. If the patient’s partner is sero-discordant, consider discussion of PrEP (refer to Treatment: Primary Prevention in Sexually Transmitted Diseases section). 
  • Assess emotional state and social supports.
  • Review risk behaviors for HIV, history of opportunistic infections, initial, most recent, and lifetime nadir CD4 counts and HIV viral load.
  • Document prior treatment regimens and CD4/viral load responses, side effects/toxicities.
  • If taking ART, assess medication adherence and barriers to adherence.
  • Assess co-morbidities
    • Viral hepatitis: liver disease tends to progress more rapidly in HIV/HCV or HIV/HBV co-infected patients; some NRTIs are active against HBV. 
    • CV disease: may impact med choices (protease inhibitors associated with impaired glucose tolerance, dyslipidemia).
    • TB: HIV infection is a significant risk factor for reactivation of latent TB, as well as for accelerated TB progression and extra-pulmonary involvement.
    • STIs: Syphilis, HSV, GC/CT, genital/anal warts/HPV.
  • Physical examination with special attention to skin, fat distribution, oral mucosa, lymphadenopathy, anogenital exam, neurologic exam.

Lab testing in HIV-infected adults

CD4 count

Entry into care, then every 3-6 months. Repeat at ART initiation/modification or if treatment failure. If clinically stable with suppressed viral load and CD4 > 500 x > 2 years CD4 testing is optional (unless viral load testing is positive).

HIV viral load

Entry into care, then every 3-6 months. Repeat at ART initiation/modification or if treatment failure. If HIV RNA detectable at 2-8 weeks of therapy, repeat q4-8 weeks until suppression <200 copies/mL. 

Resistance testing

Entry into care, ART initiation/modification, or if treatment failure. If switching therapy for toxicity or convenience, no need to re-test (genotype testing can’t be done when VL <1000 copies/mL). 

Basic chemistry, AST/ALT/Tbili 

Entry into care, ART initiation/modification, 2-8 weeks post-ART initiation/modification, and then q6-12 months. 

CBC with diff

Entry into care, ART initiation/modification, 2-8 weeks post-ART initiation/modification only if on zidovudine, then q3-6 months.

Fasting lipids

Entry into care & at ART initiation/modification. Consider repeat at 4-8 wks after new regimen that affects lipids. If normal, repeat annually. If abnormal, repeat q6 months. 

Fasting glucose or A1c

Entry into care & at ART initiation/modification. If normal, repeat q12 months. If abnormal, repeat q3-6 months.

Urinalysis

Entry into care & at ART initiation/modification. Q12 months thereafter unless on tenofovir (q6 months on tenofovir). 

Pregnancy test

Must test if starting efavirenz. Would also test for all ART with pregnancy class unknown or at initiation of HAART for all women with any risk for pregnancy.

Toxoplasma IgG titer

Entry into care to identify patients at risk for reactivation infection.

Hepatitis testing

Hep B at entry into care, ART initiation/modification, and prior to starting HCV DAA. Hep C at entry into care and q12 months for at-risk patients

TB testing

Entry into care with PPD or Quantiferon testing. Repeat if advanced HIV with initially negative results but CD4 count rise to >200 after ART. 

CMV testing

Entry into care, check anti-CMV IgG in patients at low risk of CMV (do not test MSM or IDU who are likely to be positive). If CD4 count <100 cells/mm3, consider referral to Ophtho to rule out CMV retinitis.

Syphilis testing

Entry into care, thereafter by risk profile.

Other STD testing

Entry into care: trichomoniasis in all women, gonorrhea and chlamydia in all men and women. Thereafter periodic STI testing is recommended based on risk profile. Consider testing for GC/chlamydia orally, in urine, and rectally based on sexual risk factors. 

Special testing

HLA-B*5701 if considering abacavir therapy

Tropism testing if considering CCR5 antagonist or if failure of CCR5 antagonist-based regimen

G6PD deficiency in patients of African, Asian, or Mediterranean descent (if considering dapsone for PCP prophylaxis)

 

  • CD4 counts versus percentages: CD4 counts vary with change in total WBC while CD4 percentages remain stable.

 

CD4 percentage

Corresponding CD4 count

>29%

>500 cells/mm3

14-28%  

200-500 cells/mm3

<14%  

<200 cells/mm3

Management

  • Antiretroviral therapy is recommended for all HIV-infected individuals to prevent disease progression and transmission.
  • Recommended therapy for treatment-naïve patients with no known resistance/wild-type virus (Per 2018 DHHS Guidelines): Two NRTIs (nucleoside reverse transcriptase inhibitor) with a third drug from one of the following classes: INSTI (integrase strand transfer inhibitor), NNRTI (non-nucleoside reverse transcriptase inhibitor), or PI (protease inhibitor) boosted with ritonavir. Once daily dosing noted below with *. Low pill burden noted below with #. 
  • INSTI-based regimens are recommended for most people with HIV
    • Dolutegravir/abacavir/lamivudine*# (only if HLA-B*5701 negative)
    • Dolutegravir + tenofovir/emtricitabine*
    • Elvitegravir/cobicistat/tenofovir/emtricitabine# (only if pre-ART CrCl >70 mL/min)
    • Raltegravir + tenofovir/emtricitabine
  • PI or NNRTI based regimens may be preferred in certain clinical situations
    • Darunavir + ritonavir + tenofovir/emtricitabine*
    • Atazanavir + ritonavir + tenofovir/emtricitabine*
    • Efavirenz/tenofovir/emtricitabine*#
    • Rilpivirine/tenofovir/emtricitabine*# (if HIV RNA <100,000 copies/mL and CD4 count >200)
  • Note that there are two different FDA approved forms of tenofovir – TAF (tenofovir alafenamide) has fewer bone and kidney toxicities than TDF (tenofovir disoproxil fumarate) Current recommended regimens for HIV treatment are for TAF, though PreP remains TDF (see separate chapter for PreP guidelines).
  • Use caution with medications used to treat opioid addiction including buprenorphine & methadone since interactions may occur.
  • For patients with highly resistant virus, always consult an HIV expert 

Selected adverse effects of antiretroviral medications

Dyslipidemia

PIs (except atazanavir, darunavir); stavudine; efavirenz 

Glucose intolerance

PIs

CAD

PIs

Lipodystrophy

All ARVs. Especially associated with stavudine and PIs except atazanavir, darunavir. 

Peripheral neuropathy

Didanosine, stavudine

Lactic acidosis

Didanosine, stavudine, zidovudine

Hepatotoxicity

Any antiretroviral, esp. NNRTIs & PIs. Fulminant hepatic failure most commonly seen with nevirapine – avoid in women with CD4 >250 and in men with CD4 >400.

Indirect hyperbilirubinemia

Atazanavir, indinavir (only need to stop meds if significant elevations distressing for cosmetic reasons)

Nephrotoxicity

Tenofovir (TDF), indinavir

Bone marrow toxicity

Tenofovir (TDF), zidovudine

 Preventative Care

  • Opportunistic infection prophylaxis
    • PCP if CD4 count <200.
    • Toxoplasmosis if CD4 count <100 & Toxoplasma IgG seropositive.
    • MAC if CD4 count <50.
    • TB if PPD ≥5 mm induration; positive interferon gamma test; hx of positive PPD without prior treatment; or contact with person with active pulmonary TB.
  • Immunizations
    • Give hepatitis B, 13-valent pneumococcal conjugate (PCV13) followed by 23-valent pneumococcal polysaccharide (PSV 23) at least 8 weeks later, and influenza vaccinations
      • Obtain post-vaccination HbsAb titer 1-6 months after series given to document immunity (lower response rate in HIV).
      • Administer a second dose of PPSV23 at least five years after the first dose of PPSV23. If the most recent dose of PPSV23 was administered before age 65 years, at age 65 years or older, administer another dose of PPSV23 at least five years after the last dose of PPSV23.
    • HPV vaccination should be given to men and women ≤26 yrs old.
    • Consider meningococcal vaccine (Based on SF DPH guidelines)
    • Consider hepatitis A vaccination with risk factors (travel to endemic area, MSM, injection drug use, chronic liver disease, clotting factor disorder.
      • Obtain Hep A total or IgG antibody level 1-2 months after series,
    • Zoster vaccine has unknown safety and efficacy in HIV-infected persons; consider the live vaccine in patients ≥60yo with CD4 ≥ 200. CurentlyCurrently, ACIP recommends the 2-dose recombinant vaccine may be given to immunocompetent individuals ≥50yo as some studies show improved efficacy in prevention of herpes zoster and post-herpetic neuralgia compared to live vaccine
    • Avoid live-attenuated vaccines in general. May consider MMR if higher CD4 count in some patients. 
  • Cervical cancer screening at initial evaluation, 6-12 months later, and then annually thereafter.
    • Women >30y may pursue HPV co-testing, though subsequent screening is in 3 years rather than 5 years.
  • Limited evidence to recommend routine anal Pap testing for anal cancer screening .
    • Note: UCSF anal dysplasia clinic recommends routine anal pap testing starting at age 25y for HIV+ MSM and HIV+ trans men who have sex with men
  • STD screening at initial evaluation, thereafter frequency based on risk stratification.
  • Check baseline bone density in post-menopausal women and in men ≥50 yrs old.
  • Be aware that patients with HIV also have increased incidence of non-AIDS-related CV disease, renal disease, liver disease, and malignancies.

Additional HIV Resources

  • UCSF National Clinicians’ Consultation Center (NCCC): Provides expert advice on preventing and treating HIV, from initiating treatment to managing advanced disease.
  • HIV InSite: Comprehensive, up-to-date information on HIV/AIDs treatment and prevention from UCSF
    • www.hivinsite.ucsf.edu

References

Aberg JA et al. 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. Clinical Infectious Diseases. 2014. 58(1): 1-10. 

Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67:103–108. DOI: http://dx.doi.org/10.15585/mmwr.mm6703a5

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf. Accessed 2/24/2018