What is the optimal timing and duration for administering Pre-Exposure Prophylaxis (PrEP) in the event of possible Human Immunodeficiency Virus (HIV) exposure?

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Last updated: May 2, 2025 • View editorial policy

From the Guidelines

Post-exposure prophylaxis (PEP) for HIV should be started as soon as possible after a potential exposure, ideally within 72 hours, and continued for 28 days. The recommended regimen typically includes three antiretroviral medications: tenofovir disoproxil fumarate (TDF) 300mg plus emtricitabine (FTC) 200mg once daily, combined with either raltegravir 400mg twice daily or dolutegravir 50mg once daily 1. PEP should be considered for significant exposures including unprotected sex, needle sharing, occupational needlestick injuries, or contact with potentially infectious bodily fluids through broken skin or mucous membranes.

Key Considerations

  • The effectiveness of PEP decreases with time, so immediate action is crucial—every hour matters.
  • Side effects may include nausea, fatigue, and headache, but these typically resolve within the first week.
  • During the 28-day treatment period, patients should practice safe behaviors to prevent potential transmission, and follow-up HIV testing should occur at baseline, 4-6 weeks, and 3 months after exposure.
  • PEP works by preventing HIV from establishing infection in the body by inhibiting viral replication during the window when the virus would otherwise begin to spread systemically.

Eligibility Assessment

  • Eligibility assessment should be based on the HIV status of the source whenever possible and may include consideration of background prevalence and local epidemiological patterns 2.
  • Exposures that may warrant HIV PEP include bodily fluids, mucous membrane, and parenteral exposures.
  • Exposures that do not require HIV PEP include when the exposed individual is already HIV positive, when the source is established to be HIV negative, and exposures to bodily fluids that do not pose a significant risk.

Special Considerations

  • If there is a concern for substantial HIV exposure within the past 72 hours, a 3-drug postexposure prophylaxis (PEP) regimen is recommended 1 for a duration of 28 days, with seamless transition to PrEP after PEP completion, if an HIV test result at the conclusion of PEP is negative.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Post-Exposure Prophylaxis (PEP) for HIV

  • PEP should be started as soon as possible after a high-risk exposure, with a recommended initiation time of within 72 hours 3
  • The duration of PEP is typically 28 days, as seen in studies using various antiretroviral regimens such as elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine 4 and raltegravir/tenofovir DF/emtricitabine 5, 6

Antiretroviral Regimens for PEP

  • A fixed-dose combination of elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine has been shown to be safe and well-tolerated for PEP, with higher regimen completion rates than more frequently dosed regimens 4
  • Raltegravir, tenofovir DF, and emtricitabine may be a useful 3-drug regimen for PEP, with a completion rate of 57% and minimal side effects 5
  • Emtricitabine/tenofovir disoproxil fumarate is also used for pre-exposure prophylaxis, but its use in PEP has been studied in combination with other agents such as raltegravir 6

Adherence and Safety

  • Adherence to PEP regimens is crucial, with studies showing completion rates ranging from 39% to 92% depending on the regimen and population 4, 5, 6
  • Common side effects of PEP regimens include nausea, diarrhea, headache, fatigue, and abdominal symptoms, but are often mild and self-limited 4, 5, 6

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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.