Duration of Non-Occupational Post-Exposure Prophylaxis (nPEP) for HIV Prevention
The recommended duration for non-occupational post-exposure prophylaxis (nPEP) regimens to prevent HIV infection is 28 days. 1, 2, 3
Evidence-Based Rationale
The 28-day duration recommendation is based on several lines of evidence:
- Animal studies demonstrate that nPEP administered within 48-72 hours and continued for 28 days can reduce the risk of acquiring HIV infection after mucosal and other nonoccupational exposures 1
- Shorter durations (3 or 10 days) have been shown to be less effective in animal models 1
- The 28-day course is designed to maximally suppress local viral replication that might occur in the days after exposure, potentially preventing a disseminated, established infection 1
Timing of Initiation
For nPEP to be effective, timing is critical:
- nPEP should be initiated as soon as possible after exposure, ideally within 24 hours 2, 3
- The maximum window for starting nPEP is 72 hours after exposure 1, 2, 3
- Efficacy decreases as time from exposure increases 1
- The initial dose should not be delayed due to pending laboratory test results 3
Medication Regimens
While the specific medications used for nPEP have evolved over time, the 28-day duration remains consistent:
Current preferred regimens for most adults and adolescents (as of 2025) include:
- Bictegravir/emtricitabine/tenofovir alafenamide OR
- Dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine) 3
Tenofovir-based regimens have shown better completion rates (72-87.5%) compared to older zidovudine-based regimens (42.1%) 4, 5
Adherence Considerations
Completing the full 28-day course is essential but challenging:
- Studies show that 17-47% of recipients do not complete the full course due to medication side effects 2
- Common side effects include nausea (26.5%), malaise and fatigue (22.8%) 2
- Strategies to improve adherence include:
- Prescribing medications with fewer doses and pills
- Providing anti-emetics for side effects
- Offering ongoing support and consultation 2
Follow-up and Monitoring
During and after the 28-day nPEP course:
- Initial follow-up at 24 hours (in person or remote) after starting nPEP 2, 3
- Clinical follow-up with laboratory testing at 4-6 weeks and 12 weeks after exposure 3
- HIV testing is recommended at 4-6 weeks and 3 months post-exposure 2
Transition to PrEP
For individuals with ongoing HIV risk:
- Those completing nPEP should be evaluated for pre-exposure prophylaxis (PrEP) to reduce risk of future exposures 3
- A transition plan from nPEP to PrEP should be created for appropriate candidates 3
Pitfalls to Avoid
- Delaying the first dose beyond 72 hours (nPEP will not be effective)
- Prescribing a shorter course than 28 days (reduced efficacy)
- Failing to address medication side effects (leads to non-completion)
- Not following up appropriately to assess for HIV seroconversion
- Missing the opportunity to transition high-risk individuals to PrEP after completing nPEP
Remember that initiating nPEP promptly and ensuring completion of the full 28-day course are crucial factors in preventing HIV infection after a high-risk exposure.