What is the recommended Post-Exposure Prophylaxis (PEP) treatment regimen for individuals potentially exposed to Human Immunodeficiency Virus (HIV)?

Recommended Post-Exposure Prophylaxis (PEP) Treatment Regimen for HIV Exposure

The current recommended PEP regimen for individuals potentially exposed to HIV is a 28-day course of tenofovir-based combinations with newer integrase inhibitors such as bictegravir or dolutegravir due to better tolerability, fewer drug interactions, and higher completion rates. 1

Initial Assessment and Timing

• PEP should be initiated as soon as possible after exposure, ideally within 72 hours
• Evaluate the exposed person's risk of infection based on exposure type
• Assess source patient's HIV status when possible (consider rapid testing)
• Do not test discarded needles or syringes for virus contamination

Recommended PEP Regimens

Current First-Line Regimen (2025 Guidelines)

• Tenofovir-based combinations with integrase inhibitors 1:
  • Tenofovir + Emtricitabine + Bictegravir (single tablet regimen)
  • Tenofovir + Emtricitabine + Dolutegravir

Alternative Regimens with Strong Evidence

• Tenofovir DF/Emtricitabine/Rilpivirine (single tablet regimen)

  • Demonstrated 86.1% completion rate in prospective studies
  • Generally well-tolerated with mostly mild to moderate adverse events 2

• Dolutegravir with Tenofovir/Emtricitabine

  • Showed 90% completion rate in studies
  • Common side effects: fatigue (26%), nausea (25%), diarrhea (21%) 3

• Bictegravir/Emtricitabine/Tenofovir Alafenamide (single tablet regimen)

  • 90.4% completion rate in recent studies
  • Lower rates of side effects compared to historical PEP regimens 4

Historical Basic Regimen (2001 Guidelines)

• Zidovudine (ZDV) + Lamivudine (3TC) (available as Combivir)
  • ZDV: 600 mg per day in two or three divided doses
  • 3TC: 150 mg twice daily 5
  • Note: This regimen has been largely replaced due to side effect profile

Monitoring and Follow-up

• Perform HIV-antibody testing at:

  • Baseline (before starting PEP)
  • 6 weeks post-exposure
  • 3 months post-exposure
  • 6 months post-exposure 5, 1

• Evaluate exposed persons taking PEP within 72 hours after exposure

• Monitor for drug toxicity for at least 2 weeks 5

• Perform additional HIV testing if symptoms of acute retroviral syndrome develop 1

Special Considerations

• Source patients with known antiretroviral resistance: Consult infectious disease specialist to select drugs to which the source's virus is unlikely to be resistant 1

• Pregnant women:

  • Avoid efavirenz due to teratogenicity risk
  • Tenofovir-based regimens are generally considered safe 1

• Medication adherence:

  • Critical for effectiveness - studies show PEP is ineffective without good adherence
  • Single tablet regimens improve adherence rates 4, 3

Common Side Effects and Management

• Gastrointestinal: Nausea (15-25%), diarrhea (7-21%)

  • Manage with antiemetics and antimotility agents as needed

• Constitutional: Fatigue (10-26%)

• Laboratory abnormalities:

  • Monitor liver enzymes (ALT elevations in up to 22%)
  • Monitor renal function (mean eGFR decrease of 14 ml/min/1.73m² observed with some regimens) 3

Prevention of Secondary Transmission

• Advise exposed persons to use precautions to prevent secondary transmission during the follow-up period
• Provide condoms and appropriate counseling

The evolution from older regimens to newer integrase inhibitor-based combinations reflects improvements in tolerability and completion rates, which are crucial for PEP effectiveness in preventing HIV infection following exposure.