What is the recommended Post-Exposure Prophylaxis (PEP) medication regimen?

Recommended Post-Exposure Prophylaxis (PEP) Medication Regimen

For HIV post-exposure prophylaxis, the recommended regimen 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

Current Preferred Regimens

First-Line Regimen

• Bictegravir/emtricitabine/tenofovir alafenamide (single tablet daily for 28 days) 1, 2
• Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (or lamivudine) 1, 2

Alternative Regimens

• Tenofovir disoproxil fumarate/emtricitabine/rilpivirine (single tablet daily for 28 days) 3
• Tenofovir disoproxil fumarate/emtricitabine plus raltegravir 1

PEP Administration Protocol

1. Initiation Timing: Start PEP as soon as possible after exposure, ideally within 24 hours but no later than 72 hours 1, 2
2. Duration: Complete full 28-day course 4, 1
3. Baseline Testing: Perform HIV antibody/antigen test before starting PEP (but do not delay PEP initiation while awaiting results) 1, 2
4. Follow-up Evaluation:
   • Initial follow-up within 72 hours of starting PEP 4
   • Monitor for drug toxicity for at least 2 weeks 4
   • HIV testing at baseline, 6 weeks, 3 months, and 6 months post-exposure 4, 1

Regimen Selection Considerations

Source Patient Factors

• If source patient has known antiretroviral resistance, consult infectious disease specialist to select appropriate drugs 4, 1
• For high-risk exposures or when source has suspected resistance, expanded regimens may be warranted 4

Special Populations

• Pregnant women: Avoid efavirenz due to teratogenicity risk; tenofovir-based regimens are generally considered safe 1
• Renal impairment: Dose adjustment may be needed with tenofovir disoproxil fumarate 5

Efficacy and Tolerability

Newer Regimens (Integrase Inhibitor-Based)

• Completion rates: 90.4% with bictegravir/emtricitabine/tenofovir alafenamide 6
• Side effects: Lower rates of nausea/vomiting (15.4%), fatigue (9.6%), and diarrhea (7.7%) 6

Older Regimens (Historical Comparison)

• Basic regimen: Zidovudine (ZDV) + Lamivudine (3TC) (Combivir) 4
  • ZDV: 600 mg per day in two or three divided doses
  • 3TC: 150 mg twice daily
• Expanded regimen: Basic regimen plus protease inhibitor (preferably lopinavir/ritonavir) 4
• Limitations: Higher side effect profile and lower completion rates 4

Common Side Effects and Management

• Gastrointestinal: Nausea, vomiting, diarrhea - manage with antiemetics and antimotility agents 4, 1
• Constitutional: Fatigue - supportive care and reassurance 1, 7
• Laboratory abnormalities: Monitor liver enzymes and renal function 1, 7

Prevention of Secondary Transmission

• Advise exposed persons to use precautions to prevent secondary transmission during the follow-up period 4
• Consider transition to PrEP for those with ongoing HIV exposure risk after completing PEP 2

Pitfalls to Avoid

• Delaying initiation: Do not wait for source patient testing results before starting PEP 1, 2
• Incomplete course: Emphasize importance of completing full 28-day regimen 1, 6
• Inadequate follow-up: Ensure proper testing schedule is followed 4, 1
• Failure to consider drug interactions: Assess potential interactions with current medications 1

The evolution of PEP regimens has moved from older zidovudine-based combinations to newer tenofovir-based regimens with integrase inhibitors, which offer better tolerability and higher completion rates, ultimately improving effectiveness in preventing HIV acquisition after exposure.