Antiretroviral Therapy & HIV Primary Care
Pick the regimen, dodge the interactions, and run the long game of HIV primary care
Baseline evaluation and rapid start
Baseline tests. At diagnosis obtain HIV RNA, CD4 count, genotypic resistance testing, HLA-B*5701, hepatitis B serologies (HBsAg, anti-HBs, anti-HBc), HCV antibody, creatinine/eGFR with urinalysis, LFTs, CBC, lipids, glucose or A1c, and a pregnancy test. Screen for syphilis, gonorrhea and chlamydia at exposed sites, latent TB (IGRA or skin test), and Toxoplasma IgG. A CCR5 tropism assay is needed only before maraviroc.
HLA-B*5701. Carriers are at high risk of abacavir hypersensitivity: fever, rash, GI upset, and respiratory symptoms, usually within the first 6 weeks and worsening with each dose. A positive test or any prior reaction permanently contraindicates abacavir, and rechallenge can cause hypotension and death.
Hepatitis B coinfection. The regimen must contain tenofovir (TDF or TAF) with emtricitabine or lamivudine, all of which suppress HBV. Lamivudine or emtricitabine as the only HBV-active drug selects resistance, and stopping these drugs can precipitate a severe hepatitis flare. Nonimmune patients without HBV should be vaccinated.
Rapid start. Starting ART the same day or within days speeds suppression and retention in care. It can begin before genotype, HLA, and HBV results return if a high-barrier regimen is used (bictegravir- or dolutegravir-based, or boosted darunavir, with a tenofovir backbone); abacavir and dolutegravir/lamivudine wait for those results. Cryptococcal and tuberculous meningitis are the main reasons to defer.
Choosing and monitoring the regimen
Preferred regimens. An integrase strand transfer inhibitor (INSTI) plus two NRTIs: bictegravir/TAF/emtricitabine as a single tablet, or dolutegravir with TAF or TDF plus emtricitabine or lamivudine. Dolutegravir/lamivudine two-drug therapy is acceptable only without HBV coinfection, without lamivudine resistance, and with viral load <500,000 copies/mL.
Monitoring. Check viral load 4–8 weeks after starting, then every 4–8 weeks until it is <50 copies/mL (usually by 12–24 weeks), then every 3–4 months, extending to every 6 months after 2 years of stable suppression.
Virologic failure. Failure is a confirmed viral load ≥200 copies/mL on therapy; an isolated low-level blip that returns to undetectable is not failure. Nonadherence is the usual cause.
- ConfirmRepeat the viral load.
- Find the reasonReview adherence, tolerability, and interactions such as polyvalent cations or acid suppressants (which impair rilpivirine and atazanavir absorption).
- Genotype on therapyTest while the failing regimen is still taken or within 4 weeks of stopping; off drugs, wild-type virus outgrows resistant strains and hides mutations. Standard assays need a viral load above roughly 500–1,000 copies/mL.
- RebuildConstruct a regimen with at least 2, preferably 3, fully active drugs, aiming again for <50 copies/mL.
Toxicities and drug interactions
TDF vs TAF. Tenofovir disoproxil fumarate produces high plasma tenofovir, injuring the proximal tubule (a Fanconi-like picture of glycosuria with normal glucose, phosphaturia, and proteinuria), lowering eGFR, and reducing bone density, though it lowers LDL. Tenofovir alafenamide concentrates the drug inside cells with low plasma levels, sparing kidney and bone at the cost of more weight gain and less LDL lowering.
| Drug | Key toxicity | Pearl |
|---|---|---|
| TDF | Proximal tubulopathy, ↓eGFR, bone loss | Lowers LDL |
| TAF | Weight gain, higher lipids | Kidney and bone sparing |
| Abacavir | Hypersensitivity in HLA-B*5701 carriers | Possible ↑MI risk |
| Zidovudine | Macrocytic anemia, neutropenia, myopathy | Still used IV at delivery |
| Efavirenz | Vivid dreams, insomnia, depression, suicidality, rash, hepatotoxicity | False-positive cannabinoid or benzodiazepine screen |
| Dolutegravir, bictegravir | Weight gain, insomnia, headache | Benign creatinine rise; chelated by cations |
| Atazanavir | Unconjugated hyperbilirubinemia, kidney stones | Needs gastric acid for absorption |
| Boosted protease inhibitors | Dyslipidemia, insulin resistance, GI upset | CYP3A4 inhibition |
Efavirenz. This NNRTI is taken at bedtime on an empty stomach to limit its CNS effects; it induces CYP3A4, has a low barrier to resistance, and is no longer a preferred first-line drug in the US.
Integrase inhibitors. Dolutegravir and bictegravir cause weight gain (greatest with TAF, in women and Black patients), insomnia, and headache. They block tubular creatinine secretion through OCT2, raising serum creatinine about 0.1–0.15 mg/dL without a true fall in GFR; cobicistat and trimethoprim do the same. Antacids and supplements containing aluminum, magnesium, calcium, iron, or zinc chelate INSTIs and can cause failure: give the INSTI 2 hours before or 6 hours after them, or take dolutegravir or bictegravir together with calcium or iron and food.
Pharmacologic boosters. Ritonavir and cobicistat boost darunavir, atazanavir, and elvitegravir by strongly inhibiting CYP3A4. Simvastatin and lovastatin are contraindicated (rhabdomyolysis); use pitavastatin or low-dose rosuvastatin or atorvastatin. Inhaled or intranasal fluticasone or budesonide accumulates, causing iatrogenic Cushing syndrome with adrenal suppression; beclomethasone is safer. Rifampin, a potent inducer, collapses protease inhibitor levels, so rifabutin with dose adjustment is used instead. Rifampin also cannot be combined with bictegravir, and dolutegravir must then be dosed twice daily.
Primary care for people with HIV
Vaccines. Live vaccines (MMR, varicella, yellow fever) are withheld when CD4 <200; MMR and varicella may be given at ≥200 to nonimmune patients. Recommended inactivated or recombinant vaccines:
- Pneumococcal conjugate vaccine: PCV20 or PCV21 alone, or PCV15 followed by PPSV23.
- Hepatitis B for all nonimmune patients, with anti-HBs checked after the series and revaccination of nonresponders.
- HPV through age 26 as a 3-dose series.
- Recombinant zoster (2 doses) for all adults with HIV.
- MenACWY as a 2-dose primary series with boosters every 5 years; Tdap; annual inactivated influenza; hepatitis A when at risk.
Cancer screening. HIV sharply raises HPV-related cancer risk. Cervical cytology begins at diagnosis (age ≥21), repeats yearly until 3 consecutive results are normal, then continues every 3 years for life rather than stopping at 65. Anal cancer screening with a digital anorectal exam and anal cytology, followed by high-resolution anoscopy when abnormal, begins at 35 in MSM and transgender women and at 45 in others.
Cardiovascular prevention. Chronic inflammation raises ASCVD risk about 1.5–2-fold. In the REPRIEVE trial, pitavastatin cut major cardiovascular events by about a third in people with HIV at low-to-moderate risk, so a moderate-intensity statin is advised for most adults aged 40–75. Pitavastatin barely touches CYP3A4. Smoking cessation is equally important.
Ongoing screening. Repeat STI testing at least yearly (every 3–6 months with ongoing risk) and screen for HCV yearly in people at continued risk.
Pregnancy
Antepartum. Continue ART throughout pregnancy; stopping risks rebound viremia and perinatal transmission. Start ART as soon as HIV is diagnosed in pregnancy, and dolutegravir-based regimens are preferred. Recheck viral load at 34–36 weeks to plan delivery.
| Viral load | Intrapartum IV zidovudine | Mode of delivery |
|---|---|---|
| <50 copies/mL | Not required | Vaginal; cesarean only for obstetric reasons |
| 50–1,000 copies/mL | Consider | Vaginal; cesarean for obstetric reasons |
| >1,000 or unknown | Yes | Scheduled cesarean at 38 weeks |
Newborn. Low-risk infants (mother suppressed near delivery) receive zidovudine prophylaxis for 2 weeks, and those at higher risk (maternal viremia near delivery) receive a multidrug regimen. Formula feeding eliminates postnatal transmission; people with sustained viral suppression on ART who wish to breastfeed should be supported through shared decision-making, with close maternal viral load and infant monitoring.