What is the recommended post-exposure prophylaxis (PEP) regimen for individuals potentially exposed to Human Immunodeficiency Virus (HIV)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: September 16, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

HIV Post-Exposure Prophylaxis (PEP) Recommendations

The current recommended first-line regimen for HIV post-exposure prophylaxis (PEP) is Bictegravir/emtricitabine/tenofovir alafenamide (single tablet) or Dolutegravir + (tenofovir alafenamide or tenofovir disoproxil fumarate) + (emtricitabine or lamivudine), which should be started as soon as possible after exposure and continued for 28 days. 1

Timing and Duration

  • PEP should be initiated as soon as possible after exposure - ideally within hours and no later than 72 hours
  • Complete 28-day course is required for effectiveness
  • Delayed initiation significantly decreases effectiveness

Recommended Regimens

First-Line Regimen

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

Alternative Regimens

  • Lamivudine (3TC) + Stavudine (d4T)
  • Didanosine (ddI) + Stavudine (d4T)
  • Zidovudine (ZDV) + Lamivudine (3TC) - available as Combivir

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

Children ≤10 years

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

Evaluation and Monitoring

Initial Assessment

  • Assess risk of infection using available information
  • Test known sources for HIV antibody (consider rapid testing)
  • For unknown sources, assess risk of exposure to HIV
  • Baseline testing for exposed person: HIV antibody, hepatitis B and C serology, creatinine, liver enzymes

Follow-up

  • 24-hour follow-up 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
  • Monitor for drug toxicity for at least 2 weeks

Adherence Support

  • Provide full 28-day prescription at initial visit
  • Offer enhanced adherence counseling
  • Discuss potential side effects and management strategies
  • Consider adherence tools

Transition to PrEP

  • Assess for ongoing HIV risk at completion of PEP
  • Transition directly from PEP to PrEP without interruption for individuals with continuing risk

Common Pitfalls to Avoid

  • Delaying initiation beyond 72 hours (ineffective)
  • Prescribing incomplete courses (reduced effectiveness)
  • Failing to consider drug resistance in source patients
  • Overlooking transition to PrEP for those with ongoing risk
  • Not providing adequate adherence support

The effectiveness of PEP is supported by animal studies, occupational exposure data, and prevention of mother-to-child transmission evidence, highlighting the importance of prompt initiation and complete adherence to the recommended regimen 1, 2. While older guidelines recommended two-drug regimens in certain circumstances 3, current evidence supports the use of three-drug regimens for all occupational exposures to HIV 2.

AI-generated content review: This response provides specific recommendations for HIV PEP based on the most recent guidelines, including specific drug regimens, timing, duration, monitoring requirements, and considerations for special populations.

References

Guideline

Post-Exposure Prophylaxis Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.