What is the recommended pre-exposure prophylaxis (PrEP) regimen for a male at risk of Human Immunodeficiency Virus (HIV) infection?

Recommended PrEP Regimens for Males at Risk of HIV Infection

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the recommended primary regimen for males at high risk of HIV infection, with alternative options including emtricitabine/tenofovir alafenamide (TAF/FTC) for men who have sex with men, and event-driven "2-1-1" dosing for MSM with infrequent sexual exposures. 1

Recommended PrEP Regimens

First-line Options:

• Daily TDF/FTC (Truvada): Recommended for all males at risk of sexual exposure to HIV (evidence rating AIa) 2
• Event-driven (2-1-1) TDF/FTC: May be considered as an alternative to daily PrEP specifically for MSM with infrequent sexual exposures (evidence rating AIa) 2, 1
  • This involves taking 2 pills 2-24 hours before sex (closer to 24 hours is preferred), then 1 pill 24 hours after the first dose, and 1 pill 24 hours later 2
• TAF/FTC (Descovy): Alternative option specifically for men who have sex with men and transgender women 1, 3
  • Shows non-inferior efficacy to TDF/FTC with improved renal and bone safety profiles 3

Long-acting Option:

• Injectable cabotegravir: Administered at 8-week intervals 1

Eligibility for PrEP

PrEP is recommended for males who:

• Have an annual HIV incidence risk of at least 2% 2, 1
• Are MSM with at least one episode of condomless anal intercourse in the past 6 months 1
• Have multiple sexual partners 1
• Are HIV-seronegative partners of HIV-infected persons who do not have viral suppression 1
• Engage in injection drug use with shared equipment 2, 1

Pre-initiation Assessment

Before starting PrEP, the following tests must be performed within 7 days:

• HIV testing with combination antigen-antibody assay (evidence rating AIII) 2, 1
• Serum creatinine with estimated creatinine clearance 2, 1
• Hepatitis B surface antigen testing 2, 1
• Comprehensive STI screening 1

Monitoring During PrEP

• HIV testing: Every 2-3 months (evidence rating AIII) 2, 1
• Creatinine level: At least every 6 months (evidence rating AIII), more frequently for patients >50 years, taking hypertension or diabetes medications, or with GFR <90 mL/min (evidence rating BIIa) 2, 1
• STI screening: Every 3 months (evidence rating AIIa) 2, 1
• Follow-up visit: 30 days after PrEP initiation to assess adverse effects and support adherence (evidence rating BIII) 2
• PrEP prescription: Should not exceed 90 days without interval HIV testing (evidence rating AIII) 2

Contraindications and Special Considerations

• Absolute contraindications:

  • Active HIV infection 1
  • Creatinine clearance <60 mL/min for TDF-based PrEP (evidence rating AIIa) 2, 1

• Relative contraindications:

  • Osteopenia or osteoporosis (particularly for TDF-based regimens) 1
  • Chronic hepatitis B virus infection (requires careful monitoring if PrEP is discontinued) 2, 1

Efficacy and Adherence

• Efficacy is highly dependent on adherence 4
• For MSM and transgender women, at least 4 of 7 doses per week are needed for protection 1
• For heterosexual men and people who inject drugs, at least 6 of 7 doses per week are needed 1
• When properly adhered to, TDF/FTC has shown efficacy of:
  • 44% risk reduction in MSM (iPrEx trial) 5
  • 75% risk reduction in heterosexual HIV-1-serodiscordant couples (Partners PrEP study) 5
  • 86% risk reduction with event-driven dosing in MSM (IPERGAY study) 6

Important Caveats and Pitfalls

1. Undiagnosed acute HIV infection: Starting PrEP during acute HIV infection can lead to resistance (typically M184V/I mutation). Always rule out acute infection before starting PrEP 1

2. Drug interactions: Be aware of potential interactions with other medications

3. Discontinuation protocol:

   • TDF/FTC should continue for 1 week after the last sexual exposure (evidence rating CIII) 2
   • For individuals with active HBV infection, discontinuation requires careful monitoring due to risk of hepatic flares 2

4. Adherence challenges: Regular adherence counseling and support are essential for effectiveness 1

5. Event-driven PrEP limitations: The 2-1-1 dosing is only recommended for MSM, not for other populations or patients with active HBV infection 2