Residency · Residency · Family Medicine
HIV Prevention and Primary Care Management
Introduction
Advances in antiretroviral therapy (ART) have transformed HIV from a terminal illness into a manageable chronic disease with near-normal life expectancy when treated early. Family physicians play a critical role in HIV prevention through screening, pre-exposure prophylaxis (PrEP), and increasingly in primary care management of people living with HIV (PLWH).
Screening
The USPSTF recommends HIV screening for all individuals aged 15 to 65, all pregnant persons, and anyone at increased risk regardless of age. Fourth-generation antigen/antibody combination tests detect both HIV-1/2 antibodies and p24 antigen, with a window period of approximately 2 to 4 weeks. A reactive screening test requires confirmatory testing with an HIV-1/HIV-2 antibody differentiation assay. Acute HIV infection should be considered in patients presenting with a mononucleosis-like illness, as p24 antigen or HIV RNA viral load may be positive before antibodies develop. Screening should be repeated annually for individuals at ongoing risk.
Pre-Exposure Prophylaxis (PrEP)
Indications
PrEP is indicated for sexually active adults at substantial risk for HIV acquisition. Risk groups include men who have sex with men (MSM), transgender individuals, persons with HIV-positive partners, those with a history of inconsistent condom use, recent STI, and injection drug use. PrEP carries a USPSTF Grade A recommendation for persons at increased risk.
Available Regimens
| PrEP Regimen | Route | Frequency | Approved Population | Key Monitoring |
|---|---|---|---|---|
| TDF/FTC (Truvada) | Oral | Daily | All populations | Renal function q6mo |
| TAF/FTC (Descovy) | Oral | Daily | MSM, transgender women | Weight, lipids |
| Cabotegravir (Apretude) | IM injection | Every 2 months | All populations | HIV test before each injection |
Oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) is taken daily and is approved for all populations. Oral emtricitabine/tenofovir alafenamide (TAF/FTC) is taken daily and is approved for MSM and transgender women but was not studied for vaginal acquisition. Injectable cabotegravir (CAB-LA) is given as an intramuscular injection every 2 months, has demonstrated superior efficacy to oral PrEP in clinical trials, and is preferred for patients with adherence challenges.
Monitoring on PrEP
HIV testing every 3 months is required, with confirmation of HIV-negative status before each prescription. Renal function with TDF-based regimens should be checked at baseline, at 3 months, and then every 6 months. STI screening for gonorrhea, chlamydia, syphilis, and hepatitis C should occur every 3 to 6 months. Adherence and risk behaviors should be assessed at each visit.
Post-Exposure Prophylaxis (PEP)
PEP should be initiated within 72 hours of potential HIV exposure, with earlier initiation being more effective. A 28-day course of three-drug ART, typically TDF/FTC plus dolutegravir or raltegravir, is prescribed. Baseline HIV testing is performed at presentation, with follow-up testing at 4 to 6 weeks and 3 months. The risk of the exposure should be assessed, with the highest risk associated with receptive anal intercourse and needlestick with a hollow-bore needle.
Primary Care Management of PLWH
Initial Evaluation
The initial evaluation includes CD4 count and HIV viral load (RNA) at baseline and to monitor treatment response. Resistance testing (genotype) should be performed before initiating or changing ART. Comprehensive metabolic panel, CBC, lipid panel, and urinalysis are obtained. Hepatitis A, B, and C serologies are checked, and latent tuberculosis screening is performed with IGRA or TST. STI screening (syphilis, gonorrhea, chlamydia), cervical cancer screening (Pap smear), and toxoplasma IgG are completed. Mental health, substance use, and social determinants of health are assessed.
Antiretroviral Therapy
All PLWH should be treated regardless of CD4 count, with rapid ART initiation as the current standard. The goal is to achieve and maintain an undetectable viral load (less than 200 copies/mL). The principle of U = U (Undetectable = Untransmittable) means that PLWH with sustained viral suppression do not sexually transmit HIV. Common initial regimens include integrase inhibitor-based combinations such as bictegravir/FTC/TAF or dolutegravir plus FTC/TDF. Adherence support is critical, and single-tablet regimens improve adherence.
Monitoring on ART
Viral load is checked at 4 weeks after initiation, then every 3 to 6 months until undetectable, and then every 6 months if stable. CD4 count is monitored until immune reconstitution, with a threshold of 200 for opportunistic infection prophylaxis discontinuation; monitoring can stop after sustained suppression with CD4 above 500. Annual metabolic screening includes lipids, glucose, renal function, and hepatic function. Bone density screening should be considered for patients on TDF or with other risk factors.
Opportunistic Infection Prophylaxis
| Infection | Prophylaxis | CD4 Threshold (Start) | Discontinue When |
|---|---|---|---|
| PCP (Pneumocystis) | TMP-SMX DS daily | <200 | CD4 >200 for ≥3 months on ART |
| Toxoplasmosis | TMP-SMX DS daily | <100 (and Toxo IgG+) | CD4 >200 for ≥3 months on ART |
| MAC | Azithromycin 1200 mg weekly | <50 | CD4 >100 for ≥3 months on ART |
Pneumocystis jirovecii pneumonia (PCP) prophylaxis with TMP-SMX is started when CD4 is below 200 and discontinued when CD4 exceeds 200 for 3 months or longer on ART. Toxoplasmosis prophylaxis with TMP-SMX is given when CD4 is below 100 and toxoplasma IgG is positive. Mycobacterium avium complex (MAC) prophylaxis with azithromycin is started when CD4 is below 50 and discontinued when CD4 exceeds 100 for 3 months or longer. Latent TB is treated with a rifampin-based regimen (checking for ART drug interactions) or isoniazid.
Immunizations
Influenza, COVID-19, pneumococcal (PCV20 or PCV15 plus PPSV23), and Tdap vaccines are administered per the standard schedule. Hepatitis A and B vaccination is given if the patient is non-immune. HPV vaccine is administered if age-eligible. Live vaccines including MMR, varicella, and live zoster should be avoided when CD4 is below 200. Recombinant zoster vaccine (Shingrix) is safe and recommended for PLWH aged 50 years and older.
Comorbidity Management
Cardiovascular disease risk is higher in PLWH, warranting aggressive lipid and blood pressure management. Certain ART agents contribute to dyslipidemia and insulin resistance. Cancer screening should account for increased risk of anal cancer, cervical cancer, and hepatocellular carcinoma. Bone health is affected, with increased osteoporosis risk, and earlier DEXA screening should be considered. Depression, anxiety, and PTSD are highly prevalent and should be screened for regularly and treated.
Key Clinical Pearls
PrEP should be offered proactively to all patients at increased risk because it is a Grade A USPSTF recommendation and should be part of routine primary care. U = U is a powerful public health message: patients with sustained undetectable viral loads do not transmit HIV sexually. Family physicians can manage stable PLWH in collaboration with infectious disease specialists, and the primary care relationship is critical for comprehensive comorbidity management. Mental health, substance use, and social determinants of health should be screened for and addressed at every visit because these are the primary barriers to ART adherence and viral suppression.
References
- USPSTF. Screening for HIV Infection. JAMA. 2019;321(23):2326-2336.
- USPSTF. PrEP for HIV Prevention. JAMA. 2023;330(8):736-745.
- 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, 2024.
- Cohen MS, et al. Antiretroviral therapy for the prevention of HIV-1 transmission (HPTN 052). N Engl J Med. 2016;375(9):830-839.