What are the choices for post-exposure prophylaxis (PEP)?

Post-Exposure Prophylaxis (PEP) Options for HIV Prevention

The preferred regimens for HIV post-exposure prophylaxis (PEP) are bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus tenofovir (alafenamide or disoproxil fumarate) plus emtricitabine or lamivudine, initiated as soon as possible within 72 hours of exposure and continued for 28 days. 1

Recommended PEP Regimens

Preferred Regimens for Adults and Adolescents (2025 CDC Guidelines)

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

Alternative Regimens

• Tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + rilpivirine (RPV) - single tablet regimen with good tolerability and completion rates 2
• Raltegravir + tenofovir DF + emtricitabine - shown to have fewer side effects than older protease inhibitor-based regimens 3
• Dolutegravir + tenofovir DF + emtricitabine - demonstrated 90% completion rate in studies 4

Cost-Effective Options

• TDF + lamivudine (3TC) can be used as a backbone regimen when cost is a concern, as lamivudine is clinically interchangeable with emtricitabine 5, 6

Timing and Duration of PEP

• PEP should be initiated as early as possible after exposure, ideally within hours and no later than 72 hours 1
• The recommended duration is 28 days of medication 1, 5
• If the source person is later determined to be HIV-negative, PEP can be discontinued 1

Follow-up and Monitoring

• Initial follow-up should occur within 24-72 hours after starting PEP 1
• Additional follow-up at 4-6 weeks and 12 weeks after exposure for laboratory testing 1
• Monitoring should include:
  • Assessment of medication adherence
  • Evaluation of side effects
  • Laboratory testing for drug toxicity (liver enzymes, renal function)
  • HIV testing at baseline, 6 weeks, and 12 weeks post-exposure 5

Special Considerations

Source with Known or Suspected Drug Resistance

• If the source person's virus is known or suspected to be resistant to one or more drugs in the standard PEP regimen:
  • Select drugs to which the source's virus is unlikely to be resistant
  • Consider adding a third or fourth drug from a different class
  • Seek expert consultation but do not delay PEP initiation 1

Pregnancy

• Pregnancy should not preclude the use of optimal PEP regimens 1
• Avoid efavirenz due to potential teratogenicity 5
• Tenofovir-based regimens are generally considered safe during pregnancy 5

Pediatric PEP

• For children ≤10 years:
  • Preferred backbone: Zidovudine (ZDV) + lamivudine (3TC)
  • Preferred third drug: Lopinavir/ritonavir (LPV/r)
  • Alternative backbones: Abacavir (ABC) + 3TC or TDF + 3TC/FTC 1, 7
• Dosing should be adjusted based on weight 5, 7

Common Side Effects and Management

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) - 20-27% 2, 3, 4
• Fatigue - 14-26% 2, 4
• Headache - 10-15% 2, 3
• Myalgia/arthralgia - 8% 3

Most side effects are mild to moderate and self-limited, rarely requiring discontinuation of therapy 2, 3, 4.

Pitfalls to Avoid

1. Delaying initiation - PEP should be started as soon as possible, even if the complete regimen is not immediately available. Start with available medications and adjust later if needed 1

2. Inadequate assessment of exposure risk - Not all exposures warrant PEP. Consider:

   • Type of bodily fluid (blood, genital secretions, CSF, etc.)
   • Route of exposure (mucous membrane, parenteral)
   • HIV status of the source when known 1

3. Poor adherence monitoring - The efficacy of PEP depends on completion of the full 28-day course. Early follow-up is essential to address side effects and ensure adherence 1, 5

4. Failure to consider PrEP after PEP - Persons completing PEP who have ongoing HIV risk should be evaluated for pre-exposure prophylaxis (PrEP) 1

5. Overlooking drug interactions - Consider potential interactions with other medications the patient may be taking 5

Remember that PEP is an urgent intervention that should be initiated promptly when indicated, with the regimen tailored to the specific clinical circumstances while following the most current guidelines.