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

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Last updated: November 4, 2025View editorial policy

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HIV Prophylaxis

For post-exposure prophylaxis (PEP), initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen within 24 hours of exposure (no later than 72 hours) and continue for 28 days. 1, 2

Post-Exposure Prophylaxis (PEP)

Timing and Initiation

  • Start PEP immediately upon presentation, ideally within 24 hours but absolutely within 72 hours of exposure—efficacy drops significantly with delayed initiation. 1, 2, 3
  • Do not delay the first dose while waiting for laboratory results. 1, 2
  • PEP is ineffective if started beyond 72 hours after exposure. 1, 3

Preferred Regimens for Adults and Adolescents

The CDC recommends two preferred options: 1, 2, 3

First-line choice:

  • Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single-tablet regimen 1, 2

Alternative preferred regimen:

  • Dolutegravir (DTG) plus tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC) 1, 2, 3

Duration

  • Complete the full 28-day course without interruption—incomplete adherence significantly reduces effectiveness. 1, 2, 3
  • Provide the entire 28-day prescription at the initial visit to improve completion rates. 2

Indications for PEP

PEP is indicated when: 1, 3

  • Exposure occurred within the past 72 hours
  • The exposure presents substantial HIV transmission risk (blood, blood-stained saliva, breast milk, genital secretions) 2, 3
  • The source person has HIV without sustained viral suppression OR their HIV/viral suppression status is unknown 1

Case-by-case determination is needed when the source's HIV status is completely unknown. 1

Laboratory Testing Protocol

At initial assessment: 1, 2

  • Rapid HIV antigen/antibody combination test (point-of-care or laboratory-based)
  • For persons with long-acting injectable PrEP exposure in past 12 months, add diagnostic HIV nucleic acid test (NAT) 1
  • Assess medical comorbidities, current medications, and drug allergies 1, 2

At 4-6 weeks: 1

  • Laboratory-based HIV Ag/Ab test plus diagnostic HIV NAT

At 12 weeks (final): 1, 3

  • Laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT

Pediatric Considerations

For children ≤10 years: 2

  • Preferred backbone: zidovudine (ZDV) + lamivudine (3TC)
  • Preferred third drug: lopinavir/ritonavir (LPV/r)

Special Populations

Pregnant women: 2

  • Administer PEP using the same regimens as other adults
  • TMP-SMX is the recommended prophylactic agent for opportunistic infections

Sexual assault survivors: 2, 3

  • Offer PEP promptly without waiting for risk assessment results
  • Provide enhanced adherence support

Infants born to HIV-infected mothers: 2

  • Administer antiretroviral prophylaxis
  • For infants whose mothers received no prepartum or intrapartum antiretroviral therapy, provide 6 weeks of zidovudine

Pre-Exposure Prophylaxis (PrEP)

Transition from PEP to PrEP

For persons with anticipated repeat or ongoing HIV exposure risk, transition directly from PEP to PrEP after completing the 28-day course. 1, 2, 3

  • Perform HIV testing at completion of PEP before starting PrEP 1, 2

PrEP Efficacy Considerations

  • Daily tenofovir disoproxil fumarate plus emtricitabine is safe and partially effective when combined with regular HIV monitoring and adherence counseling. 4
  • Adherence requirements differ by anatomical site: minimum 6 of 7 doses weekly (85% adherence) protects female genital tract tissue, while 2 of 7 doses weekly (28% adherence) protects colorectal tissue. 5

Critical Pitfalls to Avoid

Timing errors: 1, 2, 3

  • Delaying PEP initiation beyond 72 hours eliminates effectiveness
  • Waiting for laboratory results before starting the first dose

Adherence failures: 1, 2

  • Incomplete 28-day course significantly reduces effectiveness
  • Inadequate follow-up for medication adherence and toxicity monitoring

Drug interactions: 1, 2

  • Always assess current medications for potential interactions before prescribing

Stigma barriers: 2

  • Address stigma concerns proactively as they represent major barriers to PEP acceptance and adherence

References

Guideline

Post-Exposure Prophylaxis for HIV Exposure

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

HIV Prophylaxis Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Post-Exposure Prophylaxis for HIV

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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