What is the recommended regimen for HIV postexposure prophylaxis (PEP)?

HIV Post-Exposure Prophylaxis (PEP) Recommendations

The preferred HIV post-exposure prophylaxis (PEP) regimen for most adults and adolescents is bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine) for a 28-day course. 1

Timing of PEP Initiation

• PEP should be initiated as soon as possible after exposure, ideally within hours
• Maximum effectiveness when started within 24 hours of exposure
• Should not be delayed beyond 72 hours post-exposure 1, 2
• The first dose should not be delayed due to pending laboratory test results 1

Exposure Risk Assessment

PEP is indicated for exposures with potential for HIV transmission:

1. High-risk bodily fluids:

   • Blood, blood-stained saliva, genital secretions, breast milk
   • Cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids 1, 2

2. Exposure routes:

   • Mucous membrane exposure (sexual contact, splashes to eye, nose, mouth)
   • Parenteral exposures (needlestick, sharps injuries) 1, 2

3. Not indicated for:

   • Exposures to tears, non-blood-stained saliva, urine, and sweat
   • When the exposed person is already HIV positive
   • When the source is confirmed HIV negative 1, 2

Recommended PEP Regimens

Preferred Regimens for Adults and Adolescents (2025 CDC Guidelines)

1. First choice:

   • Bictegravir/emtricitabine/tenofovir alafenamide (single tablet)
   • OR
   • Dolutegravir + (tenofovir alafenamide or tenofovir disoproxil fumarate) + (emtricitabine or lamivudine) 1

2. Duration:

   • Complete 28-day course 1, 2

Special Populations

Pregnant individuals:

• Avoid efavirenz (EFV) due to teratogenic effects
• Avoid stavudine (d4T) + didanosine (ddI) combination due to risk of fatal lactic acidosis
• Avoid indinavir (IDV) near delivery due to risk of hyperbilirubinemia in newborns 1, 2

Children ≤10 years:

• Backbone: Zidovudine (ZDV) + lamivudine (3TC)
• Preferred third drug: Lopinavir/ritonavir (LPV/r) 1

Testing and Monitoring

Baseline Testing

• Rapid HIV test or laboratory-based antigen/antibody combination HIV test
• Hepatitis B and C serology
• Creatinine and liver enzymes 1, 2

Follow-up Testing

• 24-hour follow-up (remote or in-person) with provider
• Laboratory testing at 4-6 weeks and 12 weeks after exposure
• HIV antibody testing at baseline, 6 weeks, 3 months, and 6 months post-exposure 1, 2

Adherence Support

• Provide full 28-day prescription at initial visit (not starter packs)
• Offer enhanced adherence counseling
• Discuss potential side effects and management strategies
• Consider adherence tools (pill boxes, smartphone reminders) 1, 2

Transition to PrEP

• Assess for ongoing HIV risk at completion of PEP
• For individuals with continuing risk, transition directly from PEP to PrEP without interruption
• Create an nPEP-to-PrEP transition plan for those who accept PrEP 1, 2

Common Pitfalls to Avoid

1. Delayed initiation: PEP effectiveness decreases with time; never start beyond 72 hours 2

2. Incomplete course: Providing full 28-day prescription and adherence support is crucial for effectiveness 2

3. Failing to consider drug resistance: Select drugs to which resistance is unlikely when the source person's virus is known or suspected to be resistant 2

4. Unnecessary continuation: If the source is later determined to be HIV-negative, PEP can be discontinued 1, 2

5. Missing the PEP-to-PrEP transition: Individuals with ongoing HIV exposure risk should be evaluated for transition to PrEP without interruption 1, 2

HIV PEP is a critical intervention for preventing HIV acquisition after exposure. When properly administered with the recommended regimen and duration, with appropriate follow-up and consideration of transition to PrEP when indicated, PEP significantly reduces the risk of HIV transmission.