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Primary Care of the Person Living with HIV: History
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Contributor: Mary J. Kasten

HIV has transformed from an illness that resulted in one complication after another and nearly always resulted in death to a chronic illness that for most patients is more easily managed than diabetes or heart disease. Antiretroviral therapy (ART) is now simple and well-tolerated. The most important priority of HIV treatment is ensuring that people living with HIV stay on continuous, effective ART. ART, although not curative, suppresses the virus and allows the immune system to recover. Even when the CD4 count remains low, suppressive ART helps prevent opportunistic infections and other HIV related complications. Suppressive ART is important not only to the health of the individual living with HIV but is an important public health goal since people living with HIV will not transmit HIV to their sexual partners if their viral load is undetectable. A respectful, culturally appropriate patient–provider relationship is one of the most important factors in keeping people living with HIV engaged in care. Persons living with HIV deserve both excellent HIV and primary care. Some communities have providers that are experts in both, but often people living with HIV receive the best care by collaboration between their primary care provider and an HIV expert.

  • HIV
  • primary care
  • communication
  • prophylaxis
  • antiretroviral therapy

1. Introduction

Life-changing progress has been made over the past 30 years in the treatment of HIV infection. Establishing a high-quality, respectful relationship when caring for people living with HIV starts with non-judgmental and gender affirming communications. Ensuring preferred names and pronouns are used is part of the foundation for a high-quality patient–provider relationship. Understanding many sensitive life-style choices, which providers are often uncomfortable discussing with patients, is critical to providing high-quality primary care. This includes understanding the person’s sexual and drug use behavior in order to know best how to offer appropriate risk reduction counseling to reduce the risk both of acquiring other sexually transmitted infections (STIs) and blood borne diseases and how to eliminate the risk of HIV transmission to others. This information needs to be obtained in a non-judgmental manner with an explanation of why the information is important. The use of the communication technique legitimization is often helpful. A simple example of legitimization: “Many of my patients are sexually active with multiple partners, can you tell me who you have been sexually active with in the past year?”
Primary care clinicians should be familiar with HIV prevention including the use of condoms and both pre-exposure and post-exposure prophylaxis (PrEP and PEP) for HIV. Readers are referred to the respective Center for Disease Control (CDC) guidelines for further information [1][2]. Primary care clinicians need to understand that HIV-related stigma remains common and is a critical part of fighting the HIV pandemic in the US. HIV-related stigma discourages stigmatized people from obtaining HIV prevention, treatment, and care [3]. Primary care clinicians should avoid stigmatizing language and use preferred words and phrases. A simple example is avoiding the use of HIV patient and instead use person living with HIV to emphasize that the person is not in a constant state of illness and outside of a clinical context a person is not a patient. The CDC at hiv.gov has additional recommendations regarding preferred language [4].
Early diagnosis of HIV infection with prompt initiation of HIV treatment is crucial towards keeping people living with HIV healthy. Primary care clinicians should routinely discuss and be comfortable counseling their patients about HIV and other STI prevention. Screening for HIV is recommended for all pregnant persons and people between ages 15–65 by the United States Preventative Task Force (USPTF) at least once and for people at increased risk on a more frequent basis [5]. People at increased risk for acquiring HIV include men who have sex with men, people who inject drugs, commercial sex workers, and people whose sexual partner is living with HIV [6]. The American Geriatric Society also recommends screening older individuals, particularly as both the incidence and prevalence of HIV increases in the elderly [7]. Patients on PrEP for HIV need to be screened every 2–3 months [1]. Early diagnosis of HIV infection is advantageous to the individual in decreasing the likelihood they will experience HIV-related complications and benefits society. Many people, once they are diagnosed with HIV infection, change their behavior in an attempt to not transmit HIV to others [8]. Additionally, suppressive ART will ensure that HIV transmission through sex does not occur. Suppressive ART is therefore an important piece of HIV prevention efforts and has led to the public health slogan U = U or Undetectable equals Untransmissible. Multiple studies have shown that people living with HIV who are consistently undetectable on ART, with no virus being found in their blood, do not transmit HIV to their sexual partners [9][10]. The preferred screening test for people potentially living with undiagnosed chronic HIV infection is a fourth generation test combining serology and p24 antigen testing followed by automatic confirmatory testing if positive [11]. Testing for acute HIV infection requires both a serological test and a measure of HIV RNA (viral load) since serology can be negative early in infection. The HIV viral RNA (viral load) is expected to be very high (>100,000 copies/mL) in symptomatic acute HIV. The CDC has excellent guidelines for the diagnosis of HIV infection [11].

2. Antiretroviral Therapy

Treatment-naïve patients with a fully susceptible virus have many once a day options for initial ART which are usually well tolerated. Current initial recommended treatment options for most people living with HIV infection are listed in Table 1 [12]. Recommended baseline laboratory testing is outlined in Table 2 [6][12]. One does not need these results prior to starting ART but the lack of genotyping, HLAB*5701 testing, and hepatitis B testing will affect the ART chosen. Abacavir should not be started without first documenting the patient is HLAB*5701 negative [13] and if the patient is not known to be hepatitis B surface antigen negative a program that includes a Tenofovir formulation combined with Lamivudine or Emtricitabine is recommended. Ideally, renal function should be assessed prior to prescribing TDF. Once initial laboratory testing is available, the ART program started should be reviewed to ensure it is appropriate for the person living with HIV. The Department of Health and Human Services has very detailed guidelines regarding the use of antiretroviral agents in people living with HIV and is a great resource for both the primary care clinician and HIV expert [12].
Table 1. Recommended ART for most treatment-naïve patients with no known exposure to resistant virus [12]
  • Bictegravir/tenofovir alafenamide/emtricitabine (co-formulated tablet)
  • Dolutegravir/abacavir/lamivudine (co-formulated tablet)—only for individuals who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV) coinfection
  • Dolutegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF))
  • Dolutegravir/lamivudine (co-formulated tablet) (AI)—except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HBV testing or HIV genotypic resistance testing for nucleoside reverse transcriptase mutations are available
Abbreviations: antiretroviral therapy (ART); hepatitis B virus (HBV).
Table 2. Recommended laboratory testing at time of initial evaluation [6][12].
  • HIV antigen/antibody testing if written evidence of diagnosis not available or if viral load is low or undetectable
  • CD4 cell count and percentage
  • Plasma HIV RNA (HIV viral load)
  • Baseline genotypic resistance testing (integrase resistance testing is not needed unless patient has previously been on an integrase inhibitor)
  • HLAB*5701 if use of abacavir is being considered
  • Complete blood cell count with differential
  • Alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase
  • Electrolytes, blood urea nitrogen, creatinine
  • Lipid profile and blood glucose
  • Urinalysis
  • Gonorrhea and chlamydia nucleic acid amplification testing with sites based on potential exposure (e.g., urine, vaginal, rectal, oropharyngeal)
  • Trichomoniasis testing in all persons who have vaginal sex
  • Syphilis testing using local protocol (either rapid plasma regain or treponemal-specific antibody tests)
  • Latent Mycobacterium tuberculosis testing (tuberculin skin test or IGRA; IGRA preferred if history of BCG vaccination)
  • Varicella virus: anti-varicella IgG if no known history of vaccination, chicken pox, or shingles
  • Viral hepatitis A, B, and C testing: HBsAg, HBsAb, HBcAb, HCV antibody, and if positive HCV NAT for HCV RNA; HAV total or IgG antibody
  • Measles titer if not born before 1957 in the US, and no written documentation of adequate MMR vaccination, or serologic evidence of immunity. Persons born in the 1960s may have been vaccinated with a vaccine other than MMR and have waning immunity. Patients may opt to receive a booster MMR vaccine rather than checking serology.
  • Cytology: cervical Papanicolaou (Pap) test for all people living with HIV who have a cervix; and consider anal Pap test for all people living with HIV
  • Glucose-6-phosphate dehydrogenase screen for deficiency in appropriate racial or ethnic groups
  • Pregnancy test in persons of childbearing potential
  • Coccidioidomycosis serology for those living in endemic areas with CD4 <250 cells/mm3
Optional Testing to Consider
  • Serum cryptococcal antigen for persons with CD4 cell count <100/mm3
  • Serum testosterone level in cisgender males with fatigue, weight loss, loss of libido, erectile dysfunction, or depression
  • Chest radiography
Abbreviations: Bacillus Calmette–Guerin (BCG); hepatitis A virus (HAV); HBcAb, HBsAb, hepatitis B core antibody (HBcAb), (HBsAb); hepatitis B surface antigen (HBsAg); hepatitis C virus (HCV); human immunodeficiency virus (HIV); immunoglobulin G (IgG); interferon-γ release assay (IGRA); measles mumps rubella (MMR), nucleic acid test (NAT). Adapted from Melanie A. Thompson, 1,a Michael A. Horberg, 2,a Allison L. Agwu, 3 Jonathan A. Colasanti, 4 Mamta K. Jain, 5 William R. Short, 6 Tulika Singh, 7 and Judith A. Aberg 8. Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. CID Nov., https://doi.org/10.1093/cid/ciaa139 (accessed on 15 March 2022).
Following initiation of ART, a viral load should be checked in 2–6 weeks. If the patient is doing well, it should be checked every 4–8 weeks until viral suppression is achieved. Once viral levels fall below the level of detection testing, viral load follow-up can decrease to every 3–4 months, and if the patient stays undetectable for >2 years with a CD4 count >300 cells/mm3, viral load testing can decrease to every 6 months and CD4 testing can be done annually. CD4 count monitoring is now optional for people living with HIV who remain virologically suppressed and whose CD4 counts are consistently >500 cells/mm3 for at least 2 years [12]. Complete blood count, liver function testing, lipid profile, and renal function should be checked annually in most patients and depending upon the ART and baseline values may need more frequent monitoring [6][14]. Many clinicians check liver function tests, renal function, and lipids 2–4 weeks after ART initiation. Many patients with newly diagnosed HIV infection have opportunistic infections or other HIV-associated conditions that require expert treatment.

3. Immunizations 

Immunizations are an important part of primary care and an important tool for keeping people living with HIV healthy. The 13-valent pneumococcal conjugate vaccine (PCV13) should be given to all adults and adolescents living with HIV who have never received any pneumococcal vaccine. Those with CD4 >200 cells/mm3 should receive the 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks or more post the PCV13 vaccine. Those with CD4 counts <200 cells/mm3 can be given the PPSV23 vaccine 8 weeks after the PCV13 but delaying until after the CD4 count increases to >200 cells/mm3 is recommended if there is good reason to believe the CD4 count is likely to significantly improve with ART. This allows for a more robust immune response to the vaccine. The PPSV23 should not be delayed indefinitely while waiting for CD4 counts to improve in patients who do not have good immune recovery or who are poorly adherent to ART. Adults who have already received a PPSV23 should be given a PCV13 if it has been at least 1 year since the PPSV23. A repeat PPSV23 5 years after the first dose is recommended and a third dose after the age of 65 if it has been 5 years or longer since the last dose. No more than three lifetime doses of PPSV23 are recommended. [15]
Adults living with HIV should receive a two-dose series at least 8 weeks apart of a meningococcal A, C, Y, and W serogroup vaccine and revaccination every 5 years for life is recommended. Meningococcal B serogroup vaccine is not routinely recommended but can be considered for young adults living in group settings such as the general population [15].
The inactivated influenza vaccine is recommended annually for all persons living with HIV. The live-attenuated influenza vaccine is contraindicated. Tetanus, diphtherial, and pertussis vaccine recommendations are the same as for the general population. All people living with HIV should receive a COVID-19 vaccine series, and the three-dose primary series of a mRNA vaccine is currently recommended for patients with advanced HIV (CD4 < 200 cells/mm3 or <14%) followed by a 4th booster dose at least 3 months after the third dose. All persons living with HIV who have CD4 counts ≥ 200 cells/mm3 should have a booster dose 5 months after completing the mRNA two-dose series. If patients received the Johnson and Johnson COVID-19 vaccine, then a second dose ideally with a mRNA COVID-19 vaccine at least 4 weeks after the first dose and a booster dose of a mRNA vaccine at least 2 months after the 2nd dose if CD4 < 200 cells/mm3 is recommended. COVID-19 vaccination guidelines are rapidly changing, and readers are encouraged to review updated guidelines from the CDC [16].
The measles, mumps and rubella vaccine (MMR) is a live virus vaccine and should be given to unvaccinated adults with a CD4 > 200 cells/mm3 who were born in the US after 1956 or have immigrated to the US and have no evidence of immunity to MMR. The MMR vaccine is contraindicated in people living with HIV who have CD4 counts < 200 cells/mm3 or who are pregnant. Pregnancy should be delayed for at least 4 weeks after receiving the MMR. The MMR series is two doses at least one month apart [6].
People living with HIV who have no history of varicella or zoster and who have not been previously immunized against varicella should have serology against varicella assessed. People living with HIV who are varicella non-immune and have CD4 count > 200 cells/mm3 should be given two doses of the live attenuated varicella vaccine (Varivax) 3 months or more apart. Varivax is a contraindicated if CD4 < 200 cells/mm3 and in pregnancy [15]. An inactivated recombinant varicella vaccine (RZV), trade name Shingrix, is recommended to prevent reactivation of varicella/zoster in all adults over 50 years and in October of 2021 was recommended by the Advisory Committee on Immunization Practices for all adults 19 years and older who are immunosuppressed and at increased risk for varicella/zoster reactivation [17]. All adults living with HIV who are at risk of shingles should be vaccinated with RZV.

This entry is adapted from the peer-reviewed paper 10.3390/pathogens11040380

References

  1. Centers for Disease Control and Prevention: US Public Health Service: Preexposure Prophylaxis for the Prevention of HIV Infection in the United States—2021 Update: A Clinical Practice Guideline. Available online: https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021 (accessed on 17 March 2022).
  2. United States Centers for Disease Control and Prevention. Updated Guidelines for Antiretroviral Postexposure Prophylaxis after Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016. Available online: http:Stacks.cdc.gov/view/cdc/38856 (accessed on 17 March 2022).
  3. Greenwood, G.L.; Wilson, A.; Bansal, G.P.; Barnhart, C.; Barr, E.; Berzon, R.; Boyce, C.A.; Elwood, W.; Gamble-George, J.; Glenshaw, M.; et al. HIV-Stigma Research as a Priority at the national Institutes of Health. AIDS Behav. 2022, 26, 5–26.
  4. CDC HIV Stigma and Discrimination. Available online: https://www.cdc.gov/hiv/basics/hiv-stigma/index.html (accessed on 17 March 2022).
  5. US Preventive Services Task Force; Owens, D.K.; Davidson, K.W.; Krist, A.H.; Barry, M.J.; Cabana, M.; Caughey, A.B.; Curry, S.J.; Doubeni, C.A.; Epling, J.W., Jr.; et al. Screening for HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA 2019, 321, 2326.
  6. Melanie, A.; Thompson Michael, A.; Horberg Allison, L.; Agwu Jonathan, A.; Colasanti Mamta, K.; Jain William, R.; Short Tulika, S.; Aberg, J.A. Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin. Infect. Dis. 2020, 72, 778–779.
  7. Work Group for HIV and Aging Consensus Project. Summary report from the Human Immunodeficiency Virus and Aging Consensus Project: Treatment strategies for clinicians managing older individuals with the human immunodeficiency virus. J. Am. Geriatr. Soc. 2012, 60, 974–979.
  8. Cleary, P.D.; Van Devanter, N.; Rogers, T.F.; Singer, E.; Shipton-Levy, R.; Steilen, M.; Stuart, A.; Avorn, J.; Pindyck, J. Behavior changes after notification of HIV Infection. AJPH 1991, 81, 1586–1590.
  9. Cohen, M.S.; Chen, Y.Q.; McCauley, M.; Gamble, T.; Hosseinipour, M.C.; Kumarasamy, N.; Hakim, J.G.; Kumwenda, J.; Grinsztejn, B.; Pilotto, J.H.; et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N. Engl. J. Med. 2016, 375, 830–839.
  10. Cohen, M.S.; Chen, Y.Q.; McCauley, M.; Gamble, T.; Hosseinipour, M.C.; Kumarasamy, N.; Hakim, J.G.; Kumwenda, J.; Grinsztejn, B.; Pilotto, J.H.S.; et al. HPTN 052 Study Team Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 2011, 365, 493.
  11. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available online: https://doi.org/10.15620/cdc.23447 (accessed on 3 March 2022).
  12. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available online: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf (accessed on 11 December 2021).
  13. Mallal, S.; Phillips, E.; Carosi, G.; Molina, J.M.; Workman, C.; Tomazic, J.; Jägel-Guedes, E.; Rugina, S.; Kozyrev, O.; Cid, J.F.; et al. HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med. 2008, 358, 568–579.
  14. European Aids Clinical Society Guidelines 2021. Available online: https://eacs.sanfordguide.com/ (accessed on 17 March 2022).
  15. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available online: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf (accessed on 9 December 2021).
  16. CDC. COVID-19 Vaccination Clinical and Professional Resources. Available online: https://www.cdc.gov/vaccines/covid-19/index.html (accessed on 15 March 2022).
  17. Anderson, T.C.; Masters, N.B.; Guo, A.; Shepersky, L.; Leidner, A.J.; Lee, G.M.; Kotton, C.N.; Dooling, K.L. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb. Mortal. Wkly. Rep. 2022, 71, 80–84.
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