What are the recommended post‑exposure HIV prophylaxis, comprehensive STI testing, and follow‑up schedule after a single episode of unprotected sexual intercourse?

Guidelines for STI Screening After Unprotected Sex

After unprotected sexual intercourse, initiate HIV post-exposure prophylaxis (PEP) within 72 hours (ideally within 24 hours) if the exposure presents substantial HIV transmission risk, complete a 28-day antiretroviral course, and perform comprehensive STI testing at baseline, 4-6 weeks, and definitively at 12 weeks post-exposure. 1

Immediate Actions (Within 72 Hours)

HIV Post-Exposure Prophylaxis Decision

• Start PEP immediately if the sexual partner is HIV-positive without sustained viral suppression, has unknown viral suppression status, or comes from a high-prevalence population 2, 1
• Initiate treatment as soon as possible, ideally within 24 hours, but no later than 72 hours after exposure 1, 3
• Do not delay PEP initiation while waiting for HIV test results or risk assessment 4
• PEP is not indicated if you are already HIV-positive or if the source partner is definitively HIV-negative 2

Preferred PEP Regimens

• Use bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen for 28 days 1
• Alternative: dolutegravir plus (tenofovir alafenamide OR tenofovir disoproxil fumarate) plus (emtricitabine OR lamivudine) for 28 days 1
• Three-drug regimens are recommended for all nonoccupational sexual exposures 3, 5

HIV Testing Schedule

Baseline Testing (Before Starting PEP)

• Perform rapid point-of-care HIV test OR laboratory-based antigen/antibody (Ag/Ab) test, or both simultaneously 4, 1
• Laboratory-based testing increases sensitivity compared to rapid tests alone 4
• Do not use oral fluid-based rapid tests, as they are less sensitive for acute infection than blood tests 4
• If the patient refuses initial testing but risk is high, start PEP anyway 2

Follow-Up HIV Testing Timeline

• At 4-6 weeks post-exposure: Perform laboratory-based HIV Ag/Ab test PLUS nucleic acid testing (NAT) 4, 1
• At 12 weeks post-exposure: Perform laboratory-based HIV Ag/Ab test PLUS NAT for definitive confirmation 4, 1
• The 12-week timepoint is conclusive with fourth-generation tests and accounts for antiretroviral medication washout 4

Important Testing Caveats

• Antiretroviral medications from PEP can suppress viral load and delay antibody formation, potentially masking HIV infection 4
• A negative test at 4-6 weeks does not rule out HIV infection due to ongoing antiretroviral suppression effects 4
• If NAT is unavailable, laboratory-based Ag/Ab testing alone at 12 weeks will detect the vast majority of infections, though there will be a diagnostic gap for acute infections 4
• Individuals with impaired immune response or if the source has hepatitis C co-infection may require extended follow-up beyond 12 weeks, though this is rare with modern testing 4

Comprehensive STI Testing Beyond HIV

While the provided guidelines focus primarily on HIV PEP, comprehensive STI screening after unprotected sex should include:

Baseline and Follow-Up STI Panel

• Test for gonorrhea, chlamydia, syphilis, and hepatitis B at baseline 1
• Repeat STI testing at follow-up visits (4-6 weeks and 12 weeks) as bacterial STIs may have different incubation periods
• Consider hepatitis C testing, particularly if the exposure involved blood contact or the source is at high risk

Clinical Follow-Up Schedule

Required Medical Visits

• 24 hours after starting PEP: Medical provider visit for adherence support and toxicity assessment 4
• 4-6 weeks post-exposure: Clinical visit for laboratory testing, adherence monitoring, and toxicity evaluation 4, 1
• 12 weeks post-exposure: Final clinical visit for definitive HIV testing and STI screening 4, 1

Monitoring During PEP

• Assess medication adherence at each visit, as 78% completion rates have been documented 6
• Monitor for drug toxicity and side effects throughout the 28-day course 1, 3
• Evaluate for drug interactions with current medications 1

Risk Reduction Counseling

• Provide individualized risk-reduction counseling at the initial visit and throughout follow-up 6
• If ongoing HIV exposure risk exists, consider transitioning from PEP to pre-exposure prophylaxis (PrEP) after completing the 28-day PEP course and confirming HIV-negative status 1
• Counsel about preventing secondary transmission during the follow-up period 5

Common Pitfalls to Avoid

• Delaying PEP initiation beyond 72 hours significantly reduces effectiveness 1
• Failing to complete the full 28-day PEP course reduces protection 1
• Using oral fluid rapid tests instead of blood-based tests in the PEP context 4
• Assuming a negative test at 4-6 weeks rules out HIV infection 4
• Not considering drug interactions with the patient's current medications 1
• Failing to provide adequate follow-up for adherence support and toxicity monitoring 1