What is the recommended approach for HIV (Human Immunodeficiency Virus) prophylaxis?

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Last updated: October 22, 2025View editorial policy

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HIV Prophylaxis: Recommended Approaches

HIV prophylaxis should be initiated as soon as possible after exposure, ideally within 24 hours but no later than 72 hours, and continued for a full 28 days using a three-drug regimen of bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus tenofovir with emtricitabine/lamivudine. 1, 2

Types of HIV Prophylaxis

There are two main approaches to HIV prophylaxis:

1. Post-Exposure Prophylaxis (PEP)

  • Indicated when there has been a potential exposure to HIV within the past 72 hours 3, 1
  • Should be initiated as early as possible, ideally within 24 hours of exposure 1, 2
  • Exposures warranting PEP include contact with blood, blood-stained saliva, breast milk, genital secretions, and other high-risk bodily fluids 3
  • Not recommended when the exposed individual is already HIV-positive or when the source is confirmed HIV-negative 3

2. Pre-Exposure Prophylaxis (PrEP)

  • Recommended for individuals with ongoing risk of HIV exposure 4
  • Transition from PEP to PrEP should be considered for persons with anticipated repeat or ongoing HIV exposure risk 1, 2
  • Has been shown to be cost-effective in high-risk populations 5

Recommended PEP Regimens

Adults and Adolescents

  • Preferred regimens: 1, 2
    • Bictegravir/emtricitabine/tenofovir alafenamide (single-tablet regimen)
    • Dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine)

Children ≤10 years

  • Preferred backbone: Zidovudine (ZDV) + lamivudine (3TC) 3
  • Preferred third drug: Lopinavir/ritonavir (LPV/r) 3
  • Alternative regimens include abacavir + lamivudine or tenofovir + lamivudine/emtricitabine 3

PEP Implementation Protocol

  1. Initial Assessment: 3, 1

    • Perform rapid HIV testing using antigen/antibody combination test
    • Assess for medical comorbidities, current medications, and allergies
    • Do not delay first dose while awaiting test results
  2. Timing: 1, 2

    • Start PEP as soon as possible after exposure, ideally within 24 hours
    • PEP must be initiated within 72 hours of exposure for effectiveness
  3. Duration: 3, 1

    • Complete full 28-day course of antiretroviral therapy
    • Provide the full 28-day prescription at initial assessment to improve completion rates
  4. Follow-up Testing: 1, 2

    • Interim HIV testing at 4-6 weeks post-exposure
    • Final HIV testing at 12 weeks post-exposure using laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT

Special Populations

Pregnant Women

  • PEP should be administered to pregnant women as for other adults 3
  • TMP-SMZ is the recommended prophylactic agent for opportunistic infections; dapsone is an alternative 3
  • Some providers may withhold prophylaxis during the first trimester due to theoretical concerns about teratogenicity 3

Sexual Assault Survivors

  • PEP should be offered promptly without waiting for risk assessment results 2, 6
  • Enhanced adherence support is crucial as many survivors have difficulties completing the full PEP course 6
  • Consultation with a sexual assault forensic examiner or nurse is recommended when available 6

HIV-Exposed Infants

  • Infants born to HIV-infected mothers should receive prophylaxis with antiretroviral drugs 3
  • For infants born to women who have not received prepartum or intrapartum ARV therapy, prophylaxis with 6 weeks of zidovudine is recommended 3

Common Pitfalls and Considerations

  • Delayed initiation: Effectiveness decreases significantly when PEP is started beyond 72 hours after exposure 1, 2
  • Incomplete adherence: The full 28-day course must be completed for maximum effectiveness 1, 3
  • Drug interactions: Always assess for potential interactions with the patient's current medications 1
  • Inadequate follow-up: Proper monitoring for medication adherence and toxicity is essential 1
  • Stigma concerns: Stigma has been identified as a major barrier to PEP acceptance and adherence, particularly in certain populations 7

Transition from PEP to PrEP

  • After completing PEP, individuals with ongoing HIV risk should be evaluated for transition to PrEP 1, 2
  • HIV testing should be performed at the completion of PEP before initiating PrEP 1
  • PrEP has been shown to be highly cost-effective for high-risk populations 5

References

Guideline

Post-Exposure Prophylaxis for HIV Exposure

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Post-Exposure Prophylaxis for HIV

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A Cost-effectiveness Analysis of Preexposure Prophylaxis for the Prevention of HIV Among Los Angeles County Men Who Have Sex With Men.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016

Guideline

Profilaxis de VIH en Abuso Sexual

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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