When should PEP (Post-Exposure Prophylaxis) be initiated for possible HIV (Human Immunodeficiency Virus) exposure?

When to Give PEP for Possible HIV Exposure

Post-exposure prophylaxis (PEP) for HIV should be initiated as soon as possible after exposure, ideally within 24 hours, but no later than 72 hours after the exposure event. 1

Indications for PEP

Recommended (≤72 hours after exposure):

• Anal or vaginal intercourse without a condom when:
  • Source person is known to have HIV with detectable viral load or unknown viral suppression status
  • Source person has unknown HIV status but is from a high-risk population

Case-by-case determination (≤72 hours after exposure):

• Sexual exposure when source has unknown HIV status
• Needle-sharing or other significant blood/body fluid exposure with unknown source

Not recommended:

• Exposure occurred >72 hours ago
• Source person is known to have HIV with sustained viral suppression
• Oral-genital contact without a condom
• Intact condom used during intercourse
• Exposed person taking PrEP as recommended
• Source is confirmed HIV-negative

Risk Assessment Algorithm

1. Timing of exposure:

   • ≤72 hours → Continue assessment

   • 72 hours → PEP not recommended (insufficient evidence for efficacy)

2. Type of exposure:

   • Anal/vaginal intercourse without condom → High risk
   • Needle-sharing → High risk
   • Significant blood/body fluid contact with non-intact skin → Moderate risk
   • Oral-genital contact without ejaculation → Low risk

3. Source HIV status:

   • Known HIV+ with detectable viral load → PEP recommended
   • Known HIV+ with sustained viral suppression → PEP not routinely recommended
   • Unknown HIV status → Consider population prevalence and exposure risk

PEP Regimen

When indicated, the preferred regimens for adults and adolescents are:

• Bictegravir/emtricitabine/tenofovir alafenamide (single tablet regimen)
• OR
• Dolutegravir plus (tenofovir alafenamide OR tenofovir disoproxil fumarate) plus (emtricitabine OR lamivudine) 1, 2

The complete course is 28 days, and the full course should be dispensed at the initial visit rather than providing "starter packs" to improve completion rates 2.

Implementation Process

1. Initial assessment:

   • Perform rapid HIV test or laboratory-based antigen/antibody combination test
   • Do not delay first dose while awaiting test results
   • Assess for medical comorbidities, current medications, and allergies

2. Follow-up:

   • Schedule follow-up at 24 hours after starting PEP (can be remote)
   • Conduct laboratory testing at 4-6 weeks and 12 weeks after exposure
   • Final HIV tests using laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT at 12 weeks

Common Pitfalls to Avoid

• Delaying initiation beyond 72 hours significantly reduces effectiveness
• Failing to complete the full 28-day regimen reduces effectiveness
• Not considering transition to PrEP after completing PEP for those with ongoing risk
• Overlooking drug interactions or comorbidities when selecting regimen

Special Considerations

• For pregnant individuals, avoid efavirenz due to teratogenic effects
• For persons with recent long-acting injectable PrEP exposure, additional diagnostic HIV NAT is recommended at initial evaluation
• PEP should be stopped if the source is later determined to be HIV-negative

The first dose of PEP should be given as soon as possible, and the decision to continue should be reassessed once more information about the exposure and source becomes available 1, 2.