How long does a patient with possible HIV exposure need to take Post-Exposure Prophylaxis (PEP)?

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Last updated: January 23, 2026View editorial policy

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Duration of HIV Post-Exposure Prophylaxis (PEP)

The patient must complete a full 28-day course of antiretroviral therapy, regardless of exposure severity or any subsequent information about the source patient. 1, 2, 3

Critical Treatment Duration

  • PEP must be continued for exactly 28 days from initiation, with no option for early discontinuation 1
  • This 28-day duration is a good practice statement and existing recommendation that applies universally to all PEP regimens 1
  • The full course must be completed even if you later learn the source patient was HIV-negative or had undetectable viral load 2, 3

Why 28 Days Is Non-Negotiable

The 28-day duration was established through primate studies demonstrating that shorter courses fail to prevent infection after viral exposure. Animal models showed that stopping antiretrovirals before 28 days resulted in viral rebound and established infection, even when treatment was started immediately after exposure. 1, 4

Incomplete adherence to the full 28-day course significantly reduces effectiveness, making this one of the most critical aspects of PEP success 2, 3

Adherence Support Throughout the 28 Days

  • Prescribe single-tablet regimens (like bictegravir/emtricitabine/tenofovir alafenamide) whenever possible, as they improve completion rates compared to multi-pill regimens 2
  • Provide anti-emetics or other supportive medications proactively to manage side effects like nausea and fatigue 1
  • Schedule follow-up visits or phone check-ins during the 28-day course to encourage adherence and address emerging side effects 1, 2
  • Educate the patient that each dose is critical—missing doses or stopping early dramatically increases infection risk 1, 2

Follow-Up Testing Schedule After the 28-Day Course

  • At 4-6 weeks post-exposure: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT) 2, 3
  • At 12 weeks post-exposure: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV NAT 2, 3
  • If acute retroviral symptoms develop (fever, rash, lymphadenopathy) at any point, test immediately regardless of timeline 1, 5

Common Pitfall to Avoid

Never discontinue PEP early based on source patient information obtained after initiation. Even if you discover the source was HIV-negative or virally suppressed days into treatment, the patient must complete all 28 days because early viral replication may have already occurred. 2, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

HIV Post-Exposure Prophylaxis Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Post-Exposure Prophylaxis for HIV Exposure

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

HIV Testing Follow-Up After Occupational Exposure: Current Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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.

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