# HIV Antiretroviral Drugs: Life Cycle, Toxicity

> How does HIV replicate and which drug class targets each step?

From gp120 attachment to protease maturation, every antiretroviral class mapped to its step, with September 2026 US regimens, toxicities, interactions, resistance, pregnancy and PrEP.

HIV attaches to CD4 through gp120, binds a CCR5 or CXCR4 coreceptor, fuses via gp41, reverse-transcribes its RNA into DNA, integrates it, then assembles and matures as protease cleaves its polyproteins. Attachment, CCR5 and fusion inhibitors block entry, NRTIs and NNRTIs block reverse transcription, integrase inhibitors block integration, protease inhibitors block maturation, and lenacapavir targets the capsid.

## How does HIV replicate and which drug class targets each step?

Most antiretroviral questions are life-cycle questions in disguise: name the step a drug blocks, or the drug behind a toxicity.

HIV is an enveloped retrovirus carrying two copies of single-stranded RNA plus its own reverse transcriptase, integrase and protease. Envelope gp120 binds CD4 and then a coreceptor, usually CCR5 early in infection and sometimes CXCR4 later, and gp41 fuses the membranes. Error-prone reverse transcription breeds resistant variants, so monotherapy fails, and no drug removes integrated provirus, so treatment is lifelong suppression, not cure. More organism guides sit on the [Infectious Disease](/topics/infectious-disease) hub.

## The life-cycle drug map

Each row follows the virus one step further, from the cell surface to the budding particle.

| Step | Viral or host target | Drug class | Drugs | Exam pearl |
| --- | --- | --- | --- | --- |
| Attachment | gp120 binding to CD4 | Attachment inhibitor | Fostemsavir | Prodrug of temsavir; for multidrug-resistant HIV |
| Post-attachment | Host CD4 receptor | Monoclonal antibody | Ibalizumab | IV infusion every 2 weeks |
| Coreceptor binding | Host CCR5 | CCR5 antagonist | Maraviroc | Tropism assay first; boxed warning for hepatotoxicity |
| Fusion | gp41 | Fusion inhibitor | Enfuvirtide | Twice-daily injections; brand listed as discontinued in the US |
| Nuclear import and assembly | Capsid protein (p24) | Capsid inhibitor | Lenacapavir | Subcutaneous every 6 months |
| Reverse transcription | Active site | NRTIs, plus islatravir | Tenofovir, emtricitabine, lamivudine, abacavir, zidovudine | Chain terminators; need intracellular phosphorylation |
| Reverse transcription | Allosteric pocket | NNRTIs | Efavirenz, rilpivirine, doravirine, etravirine, nevirapine | Noncompetitive; inactive against HIV-2 |
| Integration | Integrase strand transfer | INSTIs (-tegravir) | Bictegravir, dolutegravir, cabotegravir, raltegravir | Chelated by polyvalent cations |
| Maturation | Protease cleaving Gag and Gag-Pol | Protease inhibitors (-navir) | Darunavir, atazanavir | Boosted by ritonavir or cobicistat |

> **If you only remember one thing:** entry (fostemsavir, ibalizumab, maraviroc, enfuvirtide) -> reverse transcription (NRTIs, NNRTIs) -> integration (**-tegravir**) -> maturation (**-navir**), with lenacapavir disrupting the capsid at several stages. Most people start bictegravir or dolutegravir plus one or two NRTIs.

## Entry inhibitors act before the virus gets inside

Fostemsavir is a prodrug of temsavir, which binds gp120 and blocks attachment to CD4; it is taken twice daily for multidrug-resistant HIV and prolongs the QTc at four times the usual dose. Ibalizumab, a monoclonal antibody against the CD4 receptor, blocks the post-attachment steps of entry.

Maraviroc also targets a host protein, the CCR5 coreceptor, so a tropism assay must first confirm CCR5-tropic virus; its boxed warning is hepatotoxicity, sometimes preceded by rash. Enfuvirtide blocks gp41-mediated fusion; its twice-daily subcutaneous injections cause site reactions in up to 98% of patients, and the Fuzeon brand is now listed as discontinued in the US. HIV-2 is intrinsically resistant to enfuvirtide and NNRTIs.

## NRTIs and NNRTIs both stop reverse transcription, in different ways

Classic NRTIs are phosphorylated inside the cell, incorporated by reverse transcriptase and, lacking a 3'-hydroxyl group, terminate the growing DNA chain. Tenofovir is the nucleotide analog, given as tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Islatravir, approved in a 2026 combination, is a translocation inhibitor: once incorporated, its triphosphate stops the enzyme from advancing. Resistance works by discrimination, as when M184V or K65R lets the enzyme reject the drug, or by excision, as when thymidine analog mutations remove it.

NNRTIs need no activation; they bind a pocket away from the catalytic site and inhibit the enzyme noncompetitively. Resistance to first-generation agents emerges quickly. Rilpivirine must be taken with a meal and needs gastric acid, and for initial therapy it requires HIV RNA of 100,000 copies/mL or less and a CD4 count of at least 200.

## Integrase inhibitors, protease inhibitors and boosters

INSTIs stop integrase from inserting viral DNA into the host chromosome. Bictegravir and dolutegravir are second-generation agents with a high barrier to resistance, raltegravir and elvitegravir are older, and cabotegravir is the long-acting injectable member.

Protease inhibitors stop HIV protease from cleaving the Gag and Gag-Pol polyproteins as the particle matures after budding, so released virions stay immature and noninfectious. Darunavir and atazanavir, the PIs still in routine use, are usually boosted by ritonavir or cobicistat, potent CYP3A4 inhibitors that raise PI levels and those of many co-prescribed drugs.

Lenacapavir binds the interface between capsid protein (p24) subunits and disrupts nuclear uptake of viral DNA, virion assembly and capsid formation. It is injected subcutaneously every 6 months, as Sunlenca for heavily treatment-experienced adults with multidrug-resistant HIV, always with other active drugs, and as Yeztugo for PrEP.

## Preferred initial regimens, September 2026

The US Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV, updated September 24, 2026, recommend three regimens for most people starting treatment.

| Regimen | Guideline status | Conditions |
| --- | --- | --- |
| Bictegravir/TAF/emtricitabine | Recommended for most people | Rifampin contraindicated |
| Dolutegravir + (TAF or TDF) + (emtricitabine or lamivudine) | Recommended for most people | Dolutegravir twice daily with rifampin |
| Dolutegravir/lamivudine | Recommended for most people, regardless of baseline viral load | Not with HBV coinfection or unknown HBV status, before a reverse transcriptase genotype, or for rapid starts |
| Boosted darunavir + (TAF or TDF) + (emtricitabine or lamivudine) | Certain clinical scenarios; recommended after cabotegravir PrEP if ART starts before integrase genotype results | Prior PrEP may have selected INSTI resistance |
| Dolutegravir/abacavir/lamivudine | Certain clinical scenarios | Only if HLA-B*5701 negative |
| Boosted darunavir + lamivudine or emtricitabine | Certain clinical scenarios | Added in 2026 to avoid tenofovir and abacavir; needs a reverse transcriptase genotype; HBV requires added entecavir |
| Rilpivirine/TAF/emtricitabine or doravirine/TDF/lamivudine | Certain clinical scenarios | Rilpivirine only if HIV RNA ≤100,000 copies/mL and CD4 >=200 |

The update dropped the baseline viral-load limit on dolutegravir/lamivudine after the DOLCE study showed similar efficacy in advanced HIV. Hepatitis B status matters because TDF, TAF, emtricitabine and lamivudine all suppress HBV, so regimens for coinfected patients should include TAF or TDF, usually with emtricitabine or lamivudine. ART timing and the meningitis exceptions are covered in [HIV and the CD4 count](/blog/hiv-aids-cd4-count-usmle).

## Long-acting and newly approved regimens

Most long-acting and newly approved regimens are switch options for people whose virus is already suppressed.

- **Cabotegravir plus rilpivirine (Cabenuva):** intramuscular injections every 1 or 2 months after at least 3 months of suppression, with no known or suspected resistance to either drug; the LATITUDE trial also favored it over oral therapy in people with adherence challenges. Rifamycins are contraindicated.
- **Doravirine/islatravir (Idvynso),** FDA-approved April 20, 2026: once daily for suppressed adults with no prior virologic failure or doravirine resistance. The tablet has no hepatitis B activity, and islatravir is contraindicated with lamivudine and emtricitabine.
- **Bictegravir/lenacapavir (Bixlenvo),** FDA-approved August 27, 2026: once daily for suppressed adults without resistance to either drug.
- **Dolutegravir/lamivudine as a switch** is not recommended with any history of M184V/I, and neither is a boosted PI plus lamivudine or emtricitabine.

## Toxicities that identify the drug

Signature adverse effects name the drug in most stems, and older agents stay exam favorites long after leaving routine practice.

| Drug | Signature toxicity | Testable detail |
| --- | --- | --- |
| Abacavir | Hypersensitivity: fever, rash, GI and respiratory symptoms | Test HLA-B*5701 first; median onset 9 days; never rechallenge |
| Zidovudine | Anemia and neutropenia from marrow suppression, macrocytosis, myopathy | Linked to lactic acidosis; still the intrapartum IV drug |
| Tenofovir disoproxil fumarate | Proximal tubulopathy with glycosuria, phosphate wasting and non-anion-gap acidosis; bone loss | TAF has fewer kidney and bone effects; TDF keeps lipids lower |
| Emtricitabine, lamivudine, TDF, TAF | Hepatitis B flare when stopped in coinfection | Emtricitabine can also discolor the skin |
| Efavirenz | Dizziness, insomnia, vivid dreams, depression, suicidal ideation | False-positive cannabinoid and benzodiazepine screens; bedtime dosing |
| Nevirapine | Severe hepatotoxicity; rash including Stevens-Johnson syndrome | Highest risk at CD4 >250 in women and >400 in men; contraindicated in occupational and nonoccupational PEP |
| Rilpivirine | Depression; QTc prolongation | Needs a meal; proton pump inhibitors contraindicated |
| Atazanavir | Jaundice from indirect hyperbilirubinemia; kidney stones; PR prolongation | Classically attributed to UGT1A1 inhibition; the rise is benign and reversible when liver enzymes are normal |
| Indinavir | Nephrolithiasis | Older PI no longer in routine use; hydration lowers the risk |
| Boosted PIs | Raised triglycerides and LDL | Insulin resistance now rarely observed, although classic questions link PIs to hyperglycemia |
| Bictegravir, dolutegravir | Weight gain; insomnia, headache, depression | Creatinine rises from blocked tubular secretion, not lower GFR |
| Cabotegravir/rilpivirine IM, lenacapavir SC | Injection-site reactions, including nodules | Over 80% with intramuscular CAB/RPV; 47-65% with lenacapavir for treatment, 69-83% in PrEP trials |

## Interactions that show up in stems

Four interaction patterns explain most stems; general inducer and inhibitor rules are on the [CYP450 inducers and inhibitors](/blog/2026-06-23-everything-you-need-to-know-about-cyp450-enzymes-inducers-inhibitors-for-step-1) page.

- **Rifampin** induces CYP3A, P-glycoprotein and UGT1A1, and its own pharmacology is in [antibiotic mechanisms and coverage](/blog/antibiotic-mechanisms-coverage-usmle). It is not recommended with boosted PIs, bictegravir, rilpivirine, doravirine, long-acting cabotegravir/rilpivirine or lenacapavir; dolutegravir goes to twice daily, efavirenz stays at 600 mg, and rifabutin 150 mg daily replaces rifampin beside a boosted PI.
- **Acid suppression** starves rilpivirine and atazanavir of the gastric acid they need. Proton pump inhibitors are contraindicated with oral rilpivirine, and H2 blockers go at least 12 hours before or 4 hours after it.
- **Polyvalent cations** chelate INSTIs: take dolutegravir or bictegravir 2 hours before or 6 hours after aluminum or magnesium antacids, or take calcium and iron supplements with it alongside food.
- **Boosters** raise CYP3A4 substrates: ritonavir is contraindicated with lovastatin and simvastatin (rhabdomyolysis), and with fluticasone it can cause Cushing syndrome. Dofetilide is contraindicated with dolutegravir and bictegravir, and dolutegravir raises metformin levels.

## Pre-treatment testing and resistance mutations

Genotype testing is recommended at entry into care and at virologic failure (HIV RNA above 200 copies/mL), drawn while the failing regimen is still being taken or within 4 weeks of stopping it. Integrase genotyping is added after any cabotegravir PrEP or INSTI-based PEP, or when transmitted INSTI resistance is suspected.

- **M184V/I** (lamivudine, emtricitabine): more than 100-fold resistance to both, lower viral fitness and partly restored zidovudine susceptibility.
- **K65R** (tenofovir): 3- to 4-fold lower tenofovir susceptibility, reduced abacavir and lamivudine activity, no zidovudine resistance, and antagonism with thymidine analog mutations.
- **Thymidine analog mutations** (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E): excise the incorporated drug.
- **K103N:** the commonest substitution when efavirenz fails; it cross-resists nevirapine.
- **Long-acting PrEP:** prior cabotegravir is a risk for INSTI resistance, and lenacapavir-resistant virus has emerged in people with undiagnosed HIV, so the Yeztugo label requires an HIV test before starting and before every injection.

After failure, the new regimen should contain two fully active drugs if one has a high resistance barrier, otherwise three. Adding a single drug to a failing regimen is not recommended.

## Pregnancy, delivery and breastfeeding

US perinatal guidance prefers bictegravir/TAF/emtricitabine, or dolutegravir plus TAF or TDF with emtricitabine or lamivudine, in pregnancy and when trying to conceive. An early Tsepamo signal from Botswana (neural tube defects in 0.30% of dolutegravir-exposed conceptions versus 0.10%) did not persist; by 2022 the rate was 0.11%, identical to other ART. Ritonavir-boosted darunavir, twice daily in pregnancy, is preferred only in situations such as prior cabotegravir PrEP, and cobicistat boosting is not recommended because its levels fall in later pregnancy.

Near delivery, give intrapartum IV zidovudine and schedule a cesarean birth at 38 weeks if HIV RNA exceeds 1,000 copies/mL or is unknown; IV zidovudine may be considered at 50-1,000 and is not required below 50 with good adherence. Newborns receive antiretroviral prophylaxis, and with sustained suppression, breastfeeding is an option after counseling.

## PrEP and PEP options

PrEP requires a confirmed negative HIV test, because PrEP drugs taken during undiagnosed infection can select resistance.

| PrEP option | Schedule | Key limits |
| --- | --- | --- |
| TDF/emtricitabine, oral | Daily | Recommended for anyone with sexual or injection drug use risk |
| TAF/emtricitabine, oral | Daily | Not for people exposed through receptive vaginal sex |
| Cabotegravir, intramuscular | Two injections 1 month apart, then every 2 months | Recommended against sexual transmission |
| Lenacapavir (Yeztugo), subcutaneous | Every 6 months after an oral and injection start | FDA-approved June 18, 2025, for sexual exposure; adults and adolescents of at least 35 kg |

In September 2025, CDC updated its 2021 PrEP guideline to strongly recommend lenacapavir every 6 months for anyone of at least 35 kg who would benefit from PrEP, and called for more research in people who inject drugs. PEP starts within 72 hours and lasts 28 days; CDC's 2025 nonoccupational PEP guideline prefers bictegravir/emtricitabine/TAF, or dolutegravir plus TAF or TDF plus emtricitabine or lamivudine. Long-acting PrEP in the prior 6 months calls for an HIV nucleic acid test, and nevirapine is contraindicated in occupational and nonoccupational PEP.

## How USMLE tests it

Most items give one clue, such as a lab value, a genotype or a co-prescribed drug, and ask for the step, the class or the next move.

- **Fever, rash, vomiting and cough 9 days after starting an abacavir-containing regimen:** abacavir hypersensitivity; stop permanently, whatever the HLA-B*5701 result.
- **Glycosuria with normal glucose and low phosphate on TDF:** proximal tubulopathy; stop TDF and use TAF or a tenofovir-free regimen.
- **Asymptomatic jaundice with normal transaminases on atazanavir:** benign indirect hyperbilirubinemia, classically from UGT1A1 inhibition; reassure.
- **Rifampin needed by a patient on bictegravir:** switch to a dolutegravir regimen dosed twice daily.

## Worked vignette: rebound after heartburn treatment

A 31-year-old man has had an undetectable viral load for 2 years on rilpivirine/TAF/emtricitabine, taken with dinner. He started daily over-the-counter omeprazole for heartburn 2 months ago, and his HIV RNA is now 4,800 copies/mL. Which mechanism best explains the rebound?

- A. CYP3A4 induction by omeprazole
- B. Higher gastric pH reducing rilpivirine absorption
- C. Chelation of rilpivirine in the gut
- D. Blocked intracellular activation of tenofovir
- E. M184V selected by emtricitabine

**Answer: B.** Rilpivirine needs gastric acid for absorption, so its label contraindicates all proton pump inhibitors. CYP3A4 induction is the rifampin mechanism, chelation is the cation-INSTI problem, PPIs do not affect tenofovir activation, and M184V would not explain a rebound timed to a new drug. With HIV RNA above 200 copies/mL, order a genotype while he is still on the regimen and stop the PPI; if acid suppression is needed, an H2 blocker can be taken at least 12 hours before or 4 hours after rilpivirine.

## Common wrong-answer traps

- **Calling maraviroc a viral-protein blocker.** It blocks the host CCR5 coreceptor.
- **Placing protease inhibitors before budding.** Protease acts during maturation.
- **Treating HIV-2 with an NNRTI.** HIV-2 is intrinsically resistant.
- **Starting dolutegravir/lamivudine before hepatitis B and genotype results.** The guidelines exclude it from rapid starts.
- **Calling a small creatinine rise on dolutegravir, bictegravir or cobicistat kidney injury.** These drugs block tubular creatinine secretion without lowering GFR.
- **Stopping TDF/emtricitabine in hepatitis B coinfection.** Severe reactivation hepatitis can follow.

## Sources

- US adult and adolescent ARV guidelines: [what's new](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new), [what to start](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/what-start-initial-combination-regimens), [optimizing ART](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/optimizing-antiretroviral-therapy), [principles](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/principles-antiretroviral-therapy), [adverse effects](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/adverse-effects-antiretroviral-agents), [Table 20 PDF](https://clinicalinfo.hiv.gov/sites/g/files/mnhszr391/files/guidelines/documents/adult-adolescent-arv/adverse-effects-adult-adolescent-arv.pdf), [drug interactions](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/drug-interactions), [drug characteristics](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/drug-characteristics-tables), [tables PDF](https://clinicalinfo.hiv.gov/sites/g/files/mnhszr391/files/guidelines/documents/adult-adolescent-arv/tables-adult-adolescent-arv.pdf), [resistance testing](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/drug-resistance-testing), [virologic failure](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/virologic-failure), [TB/HIV](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/coinfections-tuberculosis-hiv), [HBV/HIV](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/coinfections-hepatitis-b-virus-hiv), [HIV-2](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/hiv-2-infection)
- NIH OI guidelines: [tuberculosis and rifamycin dosing](https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium)
- NIH perinatal guidelines: [initial ART in pregnancy](https://clinicalinfo.hiv.gov/en/guidelines/perinatal/recommendations-arv-drugs-pregnancy-what-start-art-never-received), [intrapartum ART](https://clinicalinfo.hiv.gov/en/guidelines/perinatal/intrapartum-antiretroviral-therapyprophylaxis), [dolutegravir](https://clinicalinfo.hiv.gov/en/guidelines/perinatal/dolutegravir-tivicay-dtg), [what's new](https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new)
- NIH pediatric ARV drug pages: [abacavir](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/abacavir), [emtricitabine](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/emtricitabine), [efavirenz](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/efavirenz), [nevirapine](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/nevirapine), [zidovudine](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/zidovudine), [enfuvirtide](https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/enfuvirtide)
- Clinicalinfo glossary and drug database: [gp120](https://clinicalinfo.hiv.gov/en/glossary/gp120), [gp41](https://clinicalinfo.hiv.gov/en/glossary/gp41), [R5-tropic virus](https://clinicalinfo.hiv.gov/en/glossary/r5-tropic-virus), [lenacapavir](https://clinicalinfo.hiv.gov/en/drugs/lenacapavir/patient), [doravirine/islatravir](https://clinicalinfo.hiv.gov/en/drugs/doravirine-islatravir/patient), [bictegravir/lenacapavir](https://clinicalinfo.hiv.gov/en/drugs/bictegravir-lenacapavir/patient)
- CDC: [nonoccupational PEP recommendations, 2025](https://www.cdc.gov/mmwr/volumes/74/rr/rr7401a1.htm), [PrEP clinical guidance](https://www.cdc.gov/hivnexus/hcp/prep/index.html), [lenacapavir PrEP recommendation, 2025](https://www.cdc.gov/mmwr/volumes/74/wr/mm7435a1.htm)
- NCBI Bookshelf: [resistance to nucleoside reverse transcriptase inhibitors](https://www.ncbi.nlm.nih.gov/books/NBK2241/)

Antiretroviral facts fade fast without retrieval practice: [Practice HIV pharmacology questions on StepGenie](https://dashboard.stepgenie.app/sign-up).

## Frequently asked questions

### Which drug class blocks each step of the HIV life cycle?

Fostemsavir blocks gp120 attachment to CD4, ibalizumab binds CD4 and blocks the post-attachment steps of entry, maraviroc blocks the CCR5 coreceptor and enfuvirtide blocks gp41-mediated fusion. NRTIs and NNRTIs both inhibit reverse transcriptase, NRTIs as chain terminators and NNRTIs at an allosteric pocket. Integrase inhibitors ending in -tegravir block integration, protease inhibitors ending in -navir block maturation, and lenacapavir inhibits capsid function at several stages.

### What are the preferred initial HIV regimens in 2026?

The US adult and adolescent guidelines, updated September 24, 2026, recommend bictegravir/TAF/emtricitabine, dolutegravir plus TAF or TDF plus emtricitabine or lamivudine, or dolutegravir/lamivudine for most people. Dolutegravir/lamivudine is now recommended regardless of baseline viral load, but not with hepatitis B coinfection or unknown HBV status, before a reverse transcriptase genotype, or for rapid starts. After cabotegravir PrEP, boosted darunavir with two NRTIs is used until an integrase genotype returns.

### Which antiretroviral side effects are most tested on USMLE?

Abacavir causes a hypersensitivity reaction, so HLA-B*5701 is tested first and the drug is never restarted after a reaction. Zidovudine suppresses the marrow, tenofovir disoproxil fumarate causes proximal tubulopathy and bone loss, and efavirenz causes vivid dreams, depression and false-positive cannabinoid screens. Nevirapine causes hepatotoxicity and Stevens-Johnson syndrome, atazanavir causes benign indirect hyperbilirubinemia, indinavir causes kidney stones, and dolutegravir and bictegravir cause weight gain plus a creatinine rise that does not reflect lower GFR.

### Which HIV drugs interact with rifampin and acid suppressants?

Rifampin induces CYP3A, P-glycoprotein and UGT1A1, so it is not recommended with boosted protease inhibitors, bictegravir, rilpivirine, doravirine, long-acting cabotegravir/rilpivirine or lenacapavir. Dolutegravir is given twice daily with rifampin, efavirenz stays at 600 mg, and rifabutin replaces rifampin alongside a boosted PI. Proton pump inhibitors are contraindicated with rilpivirine, atazanavir also needs gastric acid, and products containing aluminum, magnesium, calcium or iron chelate integrase inhibitors.

### What are the current options for HIV PrEP and PEP?

PrEP options are daily oral TDF/emtricitabine, daily oral TAF/emtricitabine (not for people exposed through receptive vaginal sex), intramuscular cabotegravir every 2 months after two initiation injections, and subcutaneous lenacapavir every 6 months, FDA-approved in June 2025 and recommended by CDC since September 2025. A negative HIV test is required first. PEP starts within 72 hours and lasts 28 days, and CDC's 2025 nonoccupational guideline prefers bictegravir/emtricitabine/TAF, or dolutegravir plus TAF or TDF plus emtricitabine or lamivudine.

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