What is the most appropriate pre-exposure prophylaxis (PrEP) regimen for a high-risk HIV-negative man who has sex with men (MSM) to prevent HIV acquisition?

Pre-Exposure Prophylaxis (PrEP) for HIV Prevention in MSM

Tenofovir disoproxil fumarate and emtricitabine as PrEP with HIV testing every 3 months is the most appropriate intervention to protect HG from acquiring HIV.

Recommended PrEP Regimen

For a man who has sex with men (MSM) at high risk of HIV infection, the evidence strongly supports the following approach:

Primary Recommendation

• Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) once daily is the recommended regimen for oral PrEP (evidence rating: AIa) 1, 2
• For MSM specifically, a double dose (2 pills) of TDF/FTC is recommended on the first day (evidence rating: AIIa) 1
• HIV testing should be performed quarterly (every 3 months) rather than monthly 1, 2

Alternative Options

• For MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis, tenofovir alafenamide (TAF)/emtricitabine is an appropriate alternative (evidence rating: BIa) 1, 2
• On-demand or event-driven PrEP ("2-1-1" dosing) is an effective alternative for MSM with infrequent sexual exposures (evidence rating: AIa) 1

Monitoring Protocol

Initial Testing (Before Starting PrEP)

• Combined HIV antibody and antigen testing (evidence rating: AIa) 1
• Serum creatinine level (evidence rating: AIIa) 1
• Hepatitis B surface antigen (evidence rating: AIIa) 1
• Hepatitis C antibody testing (evidence rating: AIIa) 1
• Genital and non-genital STI screening (evidence rating: AIIa) 1

Follow-up Schedule

• First follow-up visit at 1 month to assess adherence, tolerability, and confirm HIV-negative status (evidence rating: BIII) 1
• Quarterly follow-up (every 3 months) for:
  • HIV testing (evidence rating: AIa) 1, 2
  • STI screening (evidence rating: AIIa) 1
  • Syphilis testing (evidence rating: AIIa) 1
• Every 6 months:
  • Creatinine clearance assessment (evidence rating: AIIa) 1
  • More frequent monitoring for patients >50 years or with risk factors for kidney injury (evidence rating: BIIa) 1

Important Considerations

Efficacy

TDF/FTC has demonstrated high efficacy in preventing HIV acquisition from sexual exposures when taken consistently 1, 3. The small risk of side effects is outweighed by the substantial reduction in HIV infection risk 3.

Safety Profile

• TDF/FTC is generally well-tolerated 3
• Potential side effects include small, non-progressive, and reversible declines in:
  • Glomerular filtration rate 3
  • Bone mineral density 3
• TDF-based PrEP is contraindicated in persons with creatinine clearance below 60 mL/min/1.73m² (evidence rating: AIIa) 1

Adherence

• Adherence is crucial for PrEP efficacy 1, 2
• Each visit should be used to assess and address barriers to adherence (evidence rating: BIII) 1
• PrEP prescriptions should not exceed 90 days without interval HIV testing (evidence rating: AIII) 1

Why Not Other Options

• Monthly HIV testing is not recommended by guidelines and would be unnecessarily frequent 1, 2
• Tenofovir disoproxil fumarate alone without emtricitabine is not recommended for PrEP (evidence rating: BIII) 1
• Zidovudine and lamivudine are not recommended for PrEP in any guidelines 1, 2

Conclusion

For HG, a high-risk MSM who meets new sex partners at nightclubs, the optimal PrEP regimen is daily TDF/FTC with quarterly HIV testing, combined with the recommended condom use. This approach provides the best balance of efficacy, safety, and practicality for preventing HIV acquisition.