From the Guidelines
HIV post-exposure prophylaxis (PEP) should be started as soon as possible after a potential HIV exposure, ideally within 72 hours, with a recommended regimen of a three-drug combination of tenofovir disoproxil fumarate 300mg plus emtricitabine 200mg plus either dolutegravir 50mg once daily or raltegravir 400mg twice daily, as supported by the most recent guidelines 1. The effectiveness of PEP decreases with time, so immediate initiation is crucial.
- PEP is indicated for significant exposures including needle sticks, sexual assault, condomless sex with a known HIV-positive partner, or sharing injection equipment.
- Baseline HIV testing should be performed before starting PEP, with follow-up testing at 4-6 weeks and 3 months after exposure.
- Side effects may include nausea, fatigue, and headache, which can be managed symptomatically.
- PEP works by preventing HIV from establishing infection in the body by inhibiting viral replication at multiple stages.
- For occupational exposures, the source patient should be tested for HIV if possible.
- PEP is not 100% effective, so continued use of preventive measures is important during and after the treatment period. The most recent guidelines from 2025 1 recommend initiation of a 3-drug PEP regimen for substantial HIV exposure within 72 hours, with an evidence rating of AIIa.
- Key considerations for PEP include:
- Prompt evaluation and initiation of nPEP as soon as possible after exposure
- Initiating nPEP should not be delayed pending HIV test results or additional source person risk factor assessment
- nPEP is unlikely to be effective when initiated more than 72 hours after exposure, as noted in the 2016 guidelines 1.
From the Research
HIV Post-Exposure Prophylaxis (PEP) Regimens
- The use of antiretroviral therapy as PEP has been recommended for over a decade to prevent HIV infection after high-risk exposures 2.
- Various studies have evaluated different PEP regimens, including tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/rilpivirine (RPV) 3, elvitegravir/cobicistat/TDF/FTC 4, and raltegravir/FTC/TDF 2, 5.
Efficacy and Safety of PEP Regimens
- A study evaluating TDF/FTC/RPV as PEP found that 86.1% of participants completed the 28-day treatment, with no HIV seroconversions reported at week 16 3.
- Another study comparing elvitegravir/cobicistat/TDF/FTC to historical controls found that 71% of participants completed the 28-day regimen, with no HIV infections reported 4.
- Raltegravir/FTC/TDF has also been shown to be safe and well-tolerated as PEP, with high adherence rates and no reported HIV infections 2, 5.
Adherence and Tolerability
- Adherence to PEP regimens is crucial for their effectiveness, with studies showing that single-tablet regimens can improve adherence rates 3, 4.
- Common side effects reported with PEP regimens include nausea, diarrhea, headache, and fatigue, but these are often mild and self-limited 3, 4, 2, 5.
Comparison of PEP Regimens
- A study comparing emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis found that the former was non-inferior in terms of efficacy and had improved bone mineral density and renal safety biomarkers 6.
- The choice of PEP regimen may depend on various factors, including the individual's medical history, potential drug interactions, and personal preferences 3, 4, 2, 5.