What is the CDC recommended dosing regimen for HIV Post-Exposure Prophylaxis (PEP)?

CDC Recommended HIV PEP Dosing Regimen

The CDC currently recommends bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days as the preferred HIV post-exposure prophylaxis regimen, initiated within 72 hours of exposure (ideally within 24 hours). 1, 2, 3

Preferred Regimens

First-Line Option

• Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF): One tablet once daily for 28 days 1, 2, 3
  • This is a single-tablet regimen that simplifies adherence 2
  • Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) due to improved renal and bone safety profiles 2

Alternative Preferred Regimen

• Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily: Multi-tablet regimen for 28 days 1, 2, 3
  • Can substitute tenofovir disoproxil fumarate (TDF) 300mg for TAF if TAF is unavailable, but TAF is preferred 1, 3
  • Can substitute lamivudine (3TC) 300mg for emtricitabine if needed 1, 3

Critical Timing Requirements

• Initiate PEP as soon as possible, ideally within 24 hours of exposure 3
• Must start within 72 hours maximum—efficacy decreases significantly with delayed initiation 3
• Do not delay the first dose while awaiting laboratory results or source patient testing 2, 3
• If the source is confirmed HIV-negative during the 28-day course, PEP can be stopped 2

Duration and Adherence

• Complete the full 28-day course regardless of which regimen is used 2, 3
• Incomplete adherence significantly reduces effectiveness 3
• Research demonstrates 90% completion rates with dolutegravir-based regimens 4

Renal Function Considerations

• For patients with impaired renal function, use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) 1
• Assess baseline renal function before initiating any tenofovir-based regimen 2
• TDF causes a mean estimated glomerular filtration rate decrease of 14 ml/min/1.73m² at day 28 4

Baseline and Follow-Up Testing

At Initial Visit (Before Starting PEP)

• Rapid or laboratory-based HIV antigen/antibody combination test 1, 3
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months 1, 3
• Assess renal function, current medications, allergies, and medical comorbidities 2, 3

During PEP Course

• Evaluate within 72 hours after starting PEP 1, 3
• Monitor for drug toxicity for at least 2 weeks 1, 3

Follow-Up HIV Testing

• At 4-6 weeks: HIV Ag/Ab test plus HIV NAT 1, 3
• At 12 weeks: Laboratory-based HIV Ag/Ab combination immunoassay and HIV NAT 1, 3

Common Pitfalls to Avoid

Critical Errors

• Never prescribe only two NRTIs (like tenofovir/emtricitabine alone) for PEP—this provides inadequate protection and requires a third drug (integrase inhibitor) 1
• Never use salvage therapy agents (fostemsavir, ibalizumab) for PEP—these are reserved for treatment-experienced patients with documented resistance 2
• Never delay initiation beyond 72 hours, as effectiveness drops significantly 3

Drug Interaction Assessment

• Assess for potential interactions with concurrent medications before prescribing 1, 3
• Consider different regimens if the patient has a history of antiretroviral exposure 1

Transition to PrEP After Completing PEP

• Consider immediate transition from PEP to PrEP for persons with anticipated repeat or ongoing HIV exposures 1, 3
• Perform HIV testing at completion of the 28-day PEP course before transitioning to PrEP 1, 3

Historical Context (Not Current Practice)

The 2001 CDC guidelines recommended zidovudine (ZDV) 600mg daily plus lamivudine (3TC) 150mg twice daily as the basic regimen, with expanded regimens adding protease inhibitors for high-risk exposures 5. These older regimens are no longer recommended due to inferior tolerability, higher pill burden, and the availability of more effective integrase inhibitor-based regimens. The current 2025 guidelines represent a significant advancement in simplicity and efficacy.