What is Post-Exposure Prophylaxis (PEP) for Human Immunodeficiency Virus (HIV)?

Post-Exposure Prophylaxis (PEP) for HIV

Post-exposure prophylaxis (PEP) for HIV is an antiretroviral medication regimen that should be initiated as soon as possible, ideally within 24 hours but no later than 72 hours after potential HIV exposure, and continued for 28 days to prevent HIV infection. 1

Definition and Purpose

PEP is a preventive medical intervention used after potential exposure to HIV to reduce the risk of infection. It works by inhibiting viral replication during the window period before HIV establishes itself in the body. 2

When to Use PEP

PEP should be offered in the following situations:

• Exposures that occur within the past 72 hours (ideally started within 24 hours) 1
• Exposures to bodily fluids that pose significant risk: 1
  • Blood or blood-stained fluids
  • Genital secretions
  • Breast milk
  • Cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids
• Exposure routes that warrant consideration: 1
  • Mucous membrane exposure (sexual contact, splashes to eye, nose, or mouth)
  • Parenteral exposures (needlestick injuries, sharps)
  • Non-intact skin exposure 1

When PEP is Not Indicated

PEP is not recommended in the following situations:

• When the exposed individual is already HIV-positive 1
• When the source is confirmed HIV-negative 1
• For exposures to bodily fluids that don't pose significant risk (tears, non-blood-stained saliva, urine, sweat) 1
• When more than 72 hours have passed since exposure 1

Assessment and Initiation Process

1. Rapid risk assessment: Evaluate the type of exposure and HIV status of the source when possible 1
2. HIV testing: Perform rapid HIV testing of the exposed person, but do not delay PEP while awaiting results 1
3. Immediate initiation: Start PEP as soon as possible, ideally within 24 hours 1
4. Source testing: Attempt to determine HIV status of the source when possible 1

Recommended PEP Regimens

For Adults and Adolescents (2025 CDC Guidelines):

Preferred regimens: 1

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

For Adults and Adolescents (2015 WHO Guidelines):

• TDF (tenofovir) + 3TC (lamivudine) or FTC (emtricitabine) as the backbone regimen 1
• Plus LPV/r (lopinavir/ritonavir) or ATV/r (atazanavir/ritonavir) as the preferred third drug 1

Duration and Follow-up

• Duration: Complete a full 28-day course of PEP 1
• Follow-up testing: 1
  • Initial follow-up within 24-72 hours
  • Additional follow-up at 4-6 weeks and 12 weeks after exposure
  • HIV testing can be concluded at 4 months if using newer fourth-generation combination tests 3

Special Considerations

• Transition to PrEP: For individuals with ongoing HIV risk, consider transitioning directly from PEP to PrEP after completing the PEP course and confirming HIV-negative status 1
• Pediatric considerations: PEP regimens for children should be adjusted based on weight and age-appropriate dosing 4, 5
• Sexual assault cases: PEP should be offered promptly without waiting for risk assessment results 1, 6

Common Pitfalls to Avoid

• Delaying initiation: Never delay starting PEP while waiting for test results or expert consultation 1, 6
• Incomplete adherence: Poor adherence reduces effectiveness; provide counseling and support 2, 3
• Inadequate follow-up: Ensure proper monitoring for medication side effects and HIV seroconversion 3
• Missing the 72-hour window: Emphasize the urgency of seeking care immediately after potential exposure 1

Side Effects and Management

• Common side effects include gastrointestinal symptoms (nausea, diarrhea) 2
• Side effects should be managed proactively to improve adherence 3
• Regimen modifications may be necessary if significant toxicity occurs 2