After a condom break during unprotected vaginal or anal intercourse with a partner of unknown or HIV‑positive status, what is the recommended post‑exposure prophylaxis (PEP) regimen and follow‑up testing?

Post-Exposure Prophylaxis After Sexual HIV Exposure

Start PEP immediately—within 72 hours of condom break during vaginal or anal intercourse with an HIV-positive or unknown-status partner—using bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) or dolutegravir plus tenofovir/emtricitabine for 28 days, with HIV testing at baseline, 4-6 weeks, and 12 weeks. 1

Immediate Actions (Within 72 Hours)

Initiate PEP Without Delay

• Begin antiretroviral therapy as soon as possible after exposure, ideally within hours. The 72-hour window is the absolute outer limit; efficacy decreases significantly with each passing hour. 1
• Do not wait for HIV test results or source person evaluation before starting PEP. 2
• If you cannot provide the full 28-day course immediately, dispense at minimum a 3-5 day starter pack and arrange for the remainder within 24 hours. 1

Baseline HIV Testing

• Perform both a rapid (point-of-care) HIV test AND a laboratory-based antigen/antibody (Ag/Ab) combination test at the initial visit. 1, 2
• The dual testing approach increases sensitivity for detecting pre-existing HIV infection. 2
• Critical pitfall: Never start PEP in someone who is already HIV-positive, as dual therapy leads to resistance. 3

Preferred PEP Regimens

First-Line Options (Choose One)

Option 1: Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) - one tablet daily for 28 days 1

Option 2: Dolutegravir 50mg once daily PLUS (tenofovir alafenamide 25mg OR tenofovir disoproxil fumarate 300mg) PLUS (emtricitabine 200mg OR lamivudine 300mg) - taken as separate or combination tablets daily for 28 days 1

Regimen Selection Considerations

• BIC/FTC/TAF offers single-tablet convenience with once-daily dosing, which improves adherence. 1
• Assess for renal dysfunction: if creatinine clearance <30 mL/min, avoid tenofovir-based regimens. 1
• Check for drug interactions with current medications, particularly acid-reducing agents with integrase inhibitors. 1
• For pregnancy or potential pregnancy, dolutegravir-based regimens are acceptable but require informed discussion about neural tube defect data. 1

Follow-Up Testing Schedule

24-Hour Check-In

• Contact the patient within 24 hours (phone or in-person) to confirm medication access, assess tolerability, and reinforce adherence. 1
• This early contact is critical because many patients abandon PEP within the first few days. 1

4-6 Week Testing

• Perform laboratory-based HIV Ag/Ab test PLUS diagnostic nucleic acid test (NAT). 1, 2
• Exception: Testing at 4-6 weeks may be deferred if the patient started PEP within 24 hours of exposure AND did not miss any doses. 1
• Assess for medication side effects and adherence barriers. 1
• Screen for symptoms of acute HIV infection: fever, night sweats, lymphadenopathy, rash, sore throat, myalgias. 1

12-Week Definitive Testing

• Perform both laboratory-based HIV Ag/Ab test AND diagnostic NAT. 1, 2
• This is the definitive timepoint that rules out HIV infection, accounting for antiretroviral washout effects. 2
• This 12-week testing with both Ag/Ab and NAT is conclusive and no further HIV testing is needed unless new exposures occur. 2

Critical Counseling Points

Adherence Education

• Emphasize taking medication at the same time daily without missing doses. 1
• Explain that PEP is not 100% effective, and adherence is the single most important factor for success. 1, 4
• If a dose is missed, take it as soon as remembered and continue the regular schedule. 1

Risk Reduction During PEP

• Use condoms or abstain from sex during the entire 28-day PEP course and through the 12-week testing window. 1
• If the patient acquires HIV during PEP, they can transmit it to others. 1
• Do not share injection equipment or donate blood/tissues during this period. 1

Acute HIV Syndrome Recognition

• Instruct the patient to seek immediate medical attention if they develop flu-like or mononucleosis-like symptoms: fever, rash, swollen lymph nodes, severe fatigue, or sore throat. 1
• These symptoms warrant immediate HIV testing with NAT, as acute infection carries extremely high viral loads and transmission risk. 1

Source Person Evaluation

If Source is Known HIV-Positive

• PEP is indicated regardless of the source's viral load status, unless documented sustained viral suppression is confirmed. 1
• Obtain information about the source's antiretroviral history, resistance patterns, and current viral load if available, though this should not delay PEP initiation. 1

If Source HIV Status is Unknown

• Make a case-by-case determination based on epidemiologic risk factors. 1
• Consider local HIV prevalence, the source's risk behaviors (injection drug use, multiple partners, men who have sex with men), and the exposure circumstances. 1
• When in doubt, start PEP. You can discontinue if the source tests HIV-negative. 1

If Source Tests HIV-Negative

• Stop PEP immediately if the source is definitively confirmed HIV-negative with no window period concerns. 1

Transition to PrEP

For Ongoing Risk

• If the patient has continuing HIV exposure risk (e.g., HIV-positive partner, multiple partners, injection drug use), transition directly from PEP to pre-exposure prophylaxis (PrEP) after completing the 28-day course and confirming HIV-negative status. 1, 3
• Perform HIV testing at the completion of PEP, then immediately start PrEP without a gap. 1, 3
• This immediate transition prevents the vulnerable period between PEP completion and PrEP initiation. 3

Common Pitfalls to Avoid

Timing Errors

• Do not prescribe PEP if >72 hours have elapsed since exposure. The risk of medication toxicity outweighs uncertain benefit. 1
• Do not use PEP for frequent, repeated exposures. These patients need PrEP instead. 1

Testing Mistakes

• Do not rely on rapid oral fluid tests for PEP evaluation—they are less sensitive for acute infection. 2
• Do not skip the 12-week testing, as antiretrovirals can delay seroconversion and earlier negative tests may be falsely reassuring. 2
• Do not extend testing beyond 12 weeks in routine cases with modern Ag/Ab and NAT testing. 5, 2

Adherence Failures

• Sexual assault survivors have particularly poor PEP completion rates (3-76% in various studies). 1
• Provide intensive support, remove cost barriers, and arrange close follow-up for vulnerable populations. 1