How effective is PEP at preventing HIV infection?

Post-Exposure Prophylaxis (PEP) is highly effective at preventing HIV infection if started promptly and taken correctly, with success rates exceeding 80–90% when treatment begins within 72 hours of exposure.

Effectiveness Overview

• Early initiation is critical: PEP should ideally begin within 2 hours, and absolutely no later than 72 hours after exposure. Starting treatment earlier drastically increases success by halting viral replication before HIV integrates into host DNA.
• Efficacy range: Studies and observational data indicate:
  • Around 81% reduction in infection risk among healthcare workers after occupational exposure when PEP was used.
  • Over 90% overall efficacy in preventing HIV transmission when adherence is high and initiation is prompt.
  • In large clinical reviews, only 0.5% failure rate (5.2 per 1000 users) was observed, often due to improper timing, non-adherence, or re-exposure after completing medication.

Factors Affecting Effectiveness

1. Timing of initiation: Starting PEP after 72 hours results in a sharp drop in protection because HIV replication likely reaches lymph nodes by then.
2. Adherence: Missing or stopping doses early significantly increases failure risk. Full 28-day adherence is essential for protection.
3. Type of exposure: Efficacy is higher for needlestick and single sexual exposures than for repeated high-risk exposures.
4. Drug regimen quality: Modern three-drug combinations (e.g., TDF/FTC + Dolutegravir) are preferred for superior antiviral coverage and tolerability compared to older zidovudine-based regimens.
5. Virus and patient factors: Failures can also occur with drug-resistant HIV strains or if viral load in the source person is extremely high.