What is the recommended Post-Exposure Prophylaxis (PEP) regimen for individuals potentially exposed to Human Immunodeficiency Virus (HIV)?

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Last updated: September 6, 2025View editorial policy

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HIV Post-Exposure Prophylaxis (PEP) Recommendations

The recommended HIV PEP regimen consists of a 28-day course of three antiretroviral drugs: tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) as the backbone, plus a third drug such as lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r), initiated as soon as possible but within 72 hours after exposure. 1

Eligibility for PEP

PEP should be offered to individuals with exposures that have potential for HIV transmission:

Exposures warranting PEP:

  • Bodily fluids with transmission risk:

    • Blood and blood-stained saliva
    • Genital secretions
    • Breast milk
    • Cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids 2
  • Exposure routes:

    • Mucous membrane exposure (sexual contact, splashes to eye, nose, oral cavity)
    • Parenteral exposures (needlestick, sharps injuries) 2, 1

Exposures NOT requiring PEP:

  • When the exposed individual is already HIV positive
  • When the source is confirmed HIV negative
  • Exposures to tears, non-blood-stained saliva, urine, and sweat 2

Timing of PEP Initiation

PEP should be initiated as soon as possible after exposure, ideally within hours, but no later than 72 hours. The effectiveness of PEP decreases as time from exposure increases 1.

Risk Assessment

Assessment should include:

  1. HIV status of the source (when possible)
  2. Type of exposure (percutaneous, mucous membrane, etc.)
  3. Volume of fluid involved
  4. Severity of exposure (depth of injury, etc.)

In settings with high HIV prevalence or when the source is known to be high-risk, PEP may be considered without detailed risk assessment 2.

Recommended PEP Regimen

First-line regimen:

  • Backbone: TDF + 3TC (or FTC)
  • Third drug: LPV/r or ATV/r 1

Alternative third drugs:

  • Raltegravir (RAL)
  • Darunavir/ritonavir (DRV/r)
  • Efavirenz (EFV) - avoid in women of childbearing age 1

Alternative backbone regimens:

  • Zidovudine (ZDV) + 3TC
  • Abacavir (ABC) + 3TC 1

Duration and Administration

  • Complete a full 28-day course of PEP 2, 1
  • Provide the full 28-day prescription at the initial visit 1
  • Provide enhanced adherence counseling, including discussion of potential side effects and management strategies 1

Baseline and Follow-up Testing

Baseline testing:

  • HIV antibody test
  • Hepatitis B and C serology
  • Creatinine and liver enzymes 1

Follow-up testing:

  • HIV testing at 6 weeks, 3 months, and 6 months post-exposure
  • If using fourth-generation combination HIV p24 antigen-HIV antibody test, testing may be concluded at 4 months 3
  • Monitor for drug toxicity, especially in patients with risk factors for kidney injury 1

Special Considerations

If source is later determined to be HIV-negative:

  • PEP can be discontinued 1

For pregnant individuals:

  • Evaluate risk/benefit with special consideration of drug safety in pregnancy
  • Avoid EFV during pregnancy due to teratogenic effects observed in primate studies 2
  • Avoid d4T and ddI combination during pregnancy due to risk of fatal lactic acidosis 2
  • Avoid IDV near delivery due to risk of hyperbilirubinemia in newborns 2

Common Pitfalls to Avoid

  1. Delayed initiation: Starting PEP beyond 72 hours significantly reduces effectiveness 1

  2. Incomplete adherence: Providing a full 28-day prescription and adherence support is crucial for effectiveness 1

  3. Ignoring drug resistance: When the source person's virus is known or suspected to be resistant to certain drugs, select medications to which resistance is unlikely 1

  4. Failure to transition to PrEP: For individuals with ongoing HIV exposure risk, consider transitioning directly from PEP to PrEP without interruption 1

  5. Inadequate follow-up: Schedule follow-up within 72 hours of exposure for reevaluation and potential regimen adjustment based on new information about the source 1

Remember that while PEP is an important intervention after potential HIV exposure, it should never replace primary prevention strategies such as safe sex practices and avoiding needle sharing.

References

Guideline

HIV Post-Exposure Prophylaxis (PEP) 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.

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