What is the recommended medication for post-exposure prophylaxis (PEP) in a patient exposed to Human Immunodeficiency Virus (HIV)?

Post-Exposure Prophylaxis for HIV

Start bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days immediately—ideally within 1-2 hours but no later than 72 hours after exposure—without waiting for any test results. 1, 2, 3

Preferred First-Line Regimen

The medication of choice is bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) taken as one tablet once daily for exactly 28 days. 1, 2, 3 This regimen offers superior renal and bone safety compared to older formulations, improved completion rates due to single-tablet dosing, and better overall tolerability. 2, 3

Alternative Regimen When BIC/FTC/TAF Is Unavailable

If the preferred regimen is not accessible, use dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days. 1, 2, 3 Tenofovir disoproxil fumarate (TDF) 300mg can substitute for TAF if necessary, though TAF is strongly preferred for its superior renal safety profile. 3

Critical Timing Requirements

• Initiate PEP immediately upon presentation—do not delay for HIV test results, source patient identification, risk stratification, or specialist consultation. 2, 3
• Efficacy decreases dramatically with each passing hour; the 72-hour window is an absolute maximum, beyond which PEP is not recommended. 1, 2, 3
• The first dose should be given within 24 hours ideally, as this maximizes effectiveness. 1, 3

Baseline Assessment (Performed AFTER Starting First Dose)

• Rapid or laboratory-based HIV antigen/antibody combination test to rule out pre-existing infection. 2, 3
• HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months. 2, 3
• Baseline renal function assessment before any tenofovir-based regimen. 1, 2
• Hepatitis B surface antigen (HBsAg), pregnancy test, and screening for other sexually transmitted infections. 2, 3

Mandatory 28-Day Duration

The patient must complete the full 28-day course regardless of any subsequent information about the source patient—there is no option for early discontinuation. 2, 3 Incomplete adherence significantly reduces effectiveness. 2, 3 Provide anti-emetics or supportive medications proactively to manage side effects like nausea and fatigue. 3

Follow-Up Testing Schedule

• Within 72 hours: Clinical evaluation and assessment for drug toxicity. 3
• At 4-6 weeks: Laboratory-based HIV antigen/antibody test PLUS HIV nucleic acid test (NAT). 2, 3
• At 12 weeks: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT). 2, 3
• Immediately if acute illness develops: Test for acute retroviral syndrome regardless of timeline. 2, 3

Special Population Considerations

• Impaired renal function: Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) due to improved renal and bone safety. 1, 3
• Pregnancy: Does not preclude optimal PEP regimens and should not be a reason to deny treatment; expert consultation is advised. 3 The older regimen of zidovudine plus lamivudine is considered safe for pregnant healthcare workers if modern regimens are unavailable. 1

Essential Counseling Points

• Use barrier precautions during the 28-day treatment and follow-up period to prevent secondary transmission. 2, 3
• Seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome. 2, 3
• Avoid breastfeeding during PEP and the follow-up period. 2
• Report any side effects promptly to allow for supportive management. 2

Transition to PrEP After Completing PEP

For persons with anticipated repeat or ongoing HIV exposures, consider immediate transition from PEP to PrEP after completing the 28-day course. 1, 2, 3 Perform HIV testing at completion of PEP before transitioning to ensure the patient remains HIV-negative. 1, 2, 3

Common Pitfalls to Avoid

• Never delay PEP initiation for source testing, risk assessment, or awaiting laboratory results. 2, 3
• Never use two-drug regimens (like tenofovir/emtricitabine alone) for PEP—this provides inadequate protection and requires a third drug (integrase inhibitor). 1, 2
• Never discontinue PEP early based on subsequent source patient information; the full 28 days must be completed. 2, 3
• Never prescribe older regimens (like zidovudine-based therapy from 2001 guidelines) when modern single-tablet options are available, as these have inferior tolerability and completion rates. 4, 2
• Never fail to assess for drug interactions with concurrent medications before prescribing. 3