What is the recommended post-exposure prophylaxis (PEP) regimen for individuals potentially exposed to Human Immunodeficiency Virus (HIV)?

HIV Post-Exposure Prophylaxis (PEP) Regimen Recommendations

The current recommended post-exposure prophylaxis (PEP) regimen for individuals potentially exposed to HIV is a three-drug regimen consisting of bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus tenofovir (either alafenamide or disoproxil fumarate) plus emtricitabine or lamivudine, initiated as soon as possible within 72 hours of exposure and continued for 28 days. 1

Exposure Risk Assessment

PEP should be administered based on exposure risk:

1. High-risk exposures (requiring immediate PEP):

   • Unprotected receptive anal or vaginal intercourse with HIV-positive source
   • Needle sharing with HIV-positive source
   • Significant percutaneous injury with HIV-contaminated needle/instrument

2. Moderate-risk exposures (PEP recommended):

   • Unprotected insertive anal or vaginal intercourse with HIV-positive source
   • Oral sex with ejaculation from HIV-positive source

3. Low-risk exposures (PEP generally not recommended):

   • Oral sex without ejaculation
   • Kissing
   • Contact with intact skin

Recommended PEP Regimens

Preferred Regimens (2025 Guidelines)

• First-line regimen: Bictegravir/emtricitabine/tenofovir alafenamide 1
• Alternative first-line: Dolutegravir + (tenofovir alafenamide or tenofovir disoproxil fumarate) + (emtricitabine or lamivudine) 1

Older Regimens (2005 Guidelines)

• Basic regimen: Zidovudine + Lamivudine (available as Combivir) 2
• Expanded regimen: Basic regimen plus a protease inhibitor (preferably lopinavir/ritonavir) 2

Timing and Duration

• Initiate PEP as soon as possible after exposure, ideally within 24 hours but no later than 72 hours 1
• Continue PEP for 28 days 1
• Do not delay first dose while awaiting laboratory test results 1

Laboratory Monitoring

Baseline Testing (At Initiation)

• HIV antibody/antigen test (rapid or laboratory-based) 3
• Complete blood count
• Renal and liver function tests
• Hepatitis B and C serology

Follow-up Testing

• Clinical follow-up at 24 hours (in person or remote) 1
• Laboratory testing at 4-6 weeks and 12 weeks after exposure 1
• HIV antibody testing at baseline, 6 weeks, 3 months, and 6 months post-exposure 3
• Additional HIV testing if symptoms of acute retroviral syndrome develop 3

Patient Counseling

• Advise about potential medication side effects
• Emphasize importance of adherence to full 28-day regimen
• Counsel on precautions to prevent secondary transmission during follow-up period
• Discuss transition to PrEP if ongoing risk exists 1

Special Considerations

1. Source patient with known antiretroviral resistance:

   • Consult with infectious disease specialist
   • Select drugs to which the source's virus is unlikely to be resistant 2

2. Pregnant women:

   • Avoid efavirenz due to teratogenicity risk 2
   • Tenofovir-based regimens are generally considered safe 2

3. Pediatric patients:

   • Adjust dosing based on weight
   • Consider consultation with pediatric HIV specialist

Common Pitfalls to Avoid

1. Delayed initiation: Efficacy decreases with time; start PEP as soon as possible
2. Poor adherence: Side effects may lead to discontinuation; provide supportive care
3. Inadequate follow-up: Ensure patient returns for all scheduled testing
4. Failure to consider PrEP: For individuals with ongoing risk, transition to PrEP after completing PEP 1
5. Using outdated regimens: Older regimens (zidovudine-based) have more side effects and lower completion rates 4

The evolution of PEP regimens has moved from zidovudine-based to tenofovir-based combinations, with newer integrase inhibitors (bictegravir, dolutegravir) preferred due to better tolerability, fewer drug interactions, and higher completion rates 4, 1.