What is the recommended regimen for post-exposure prophylaxis (PEP) after potential Human Immunodeficiency Virus (HIV) exposure?

HIV Post-Exposure Prophylaxis (PEP) Regimen

Initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days immediately after potential HIV exposure, starting within 1-2 hours if possible, but no later than 72 hours post-exposure. 1, 2

Preferred Medication Regimen

The CDC's first-line choice is bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) taken as one tablet once daily for 28 days. 1, 2 This regimen maximizes adherence through single-tablet dosing and demonstrates superior tolerability compared to older regimens, with a 90.4% completion rate and minimal side effects (nausea 15.4%, fatigue 9.6%, diarrhea 7.7%). 3

Alternative Regimen

• Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days is the alternative if BIC/FTC/TAF is unavailable. 1, 2
• Lamivudine (3TC) 300mg can substitute for emtricitabine if needed. 2
• Tenofovir disoproxil fumarate (TDF) 300mg can substitute for TAF, though TAF is preferred for renal and bone safety. 2

Critical Timing Requirements

Do not delay the first dose for any reason—efficacy decreases dramatically with each passing hour. 1, 2

• Ideal initiation: within 24 hours of exposure. 2
• Maximum window: 72 hours post-exposure. 1, 2
• Start PEP before laboratory results or source patient testing are available. 2
• If the source is confirmed HIV-negative during treatment, PEP can be stopped. 2

Baseline Assessment Before First Dose

Perform these tests rapidly but do not delay the first PEP dose while awaiting results: 1, 2

• Rapid or laboratory-based HIV antigen/antibody combination test. 1, 2
• Baseline renal function (creatinine, eGFR) before any tenofovir-based regimen. 1, 2
• Review current medications for drug interactions. 1, 2
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months. 2

Follow-Up Testing Schedule

• Within 72 hours: Evaluate for drug toxicity and adherence. 4, 1, 2
• At 2 weeks: Monitor for drug toxicity. 4, 1
• At 4-6 weeks: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT). 1, 2
• At 12 weeks: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV NAT. 1, 2

Duration and Adherence

Complete the full 28-day course regardless of subsequent information about the source patient. 1, 2, 5 Incomplete adherence significantly reduces effectiveness. 1, 2

Special Populations

Renal Impairment

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) for patients with creatinine clearance 30-60 mL/min or known bone density issues. 1, 5

Pregnancy

• Pregnancy does not preclude optimal PEP regimens and should not be a reason to deny PEP. 1
• Expert consultation is advised, but do not delay initiation. 1
• Zidovudine (ZDV) + lamivudine (3TC) is considered safe in pregnancy if newer regimens cannot be used. 5

Children ≤10 Years

• Preferred backbone: zidovudine (ZDV) + lamivudine (3TC) with lopinavir/ritonavir (LPV/r) as the third drug. 5

Common Pitfalls to Avoid

• Never prescribe only two NRTIs (like tenofovir/emtricitabine alone)—this provides inadequate protection and requires a third drug (integrase inhibitor). 2
• Never delay initiation beyond 72 hours, as effectiveness drops significantly. 1, 2
• Never use salvage therapy agents (fostemsavir, ibalizumab) for PEP—these are reserved for treatment-experienced patients with documented resistance. 2
• Assess for potential drug interactions before prescribing. 1, 2

Counseling and Secondary Transmission Prevention

• Advise the exposed person to use precautions (condoms, avoid blood/tissue donation) to prevent secondary transmission during the 12-week follow-up period. 4, 1, 5
• Seek immediate medical evaluation for any acute illness (fever, rash, lymphadenopathy) during follow-up, as this may indicate acute HIV infection. 4, 5

Expert Consultation Resources

• For complex cases, contact the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911, but do not delay PEP initiation while awaiting consultation. 1

Transition to PrEP After Completing PEP

• Consider immediate transition from PEP to PrEP for persons with anticipated repeat or ongoing HIV exposures. 2
• Perform HIV testing at completion of the 28-day PEP course before transitioning to PrEP. 2