What is the recommended Pre-Exposure Prophylaxis (PrEP) treatment regimen for individuals at high risk of Human Immunodeficiency Virus (HIV) infection?

Recommended Pre-Exposure Prophylaxis (PrEP) Regimens for HIV Prevention

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the primary recommended regimen for all populations at high risk of HIV infection, including cisgender women and men who have sex with men (MSM), with an evidence rating of AIa. 1 Alternative options include emtricitabine/tenofovir alafenamide (TAF/FTC) for MSM and transgender women (not for those at risk through vaginal sex) and long-acting injectable cabotegravir.

Recommended PrEP Regimens

First-line Options:

• Daily oral TDF/FTC (200mg/300mg) - Standard regimen for all populations 1
• Daily oral TAF/FTC (200mg/25mg) - Alternative for MSM and transgender women, particularly those with or at risk for kidney dysfunction, osteopenia, or osteoporosis 1, 2
• Long-acting injectable cabotegravir - Administered at 8-week intervals with 600mg intramuscularly after an initial 4-week interval separating the first 2 injections (evidence rating: AIa) 3, 1

Population-Specific Considerations:

• For cisgender women: Daily oral TDF/FTC is the only FDA-approved option 1, 4
• For MSM and transgender women: All three options are effective 1
• For people who inject drugs: Daily oral TDF/FTC is recommended 1, 5

Baseline Testing Before PrEP Initiation

Before starting PrEP, the following tests must be performed within 7 days of initiation 3, 1:

• HIV testing with combination antigen-antibody assay
• Serum creatinine with estimated creatinine clearance
• Hepatitis B surface antigen testing
• Comprehensive STI screening
• HIV RNA testing if acute HIV infection is suspected

PrEP Initiation Protocol

1. Same-day initiation is possible if a negative HIV test result (within 7 days) is available and there are no symptoms of primary HIV infection 3
2. If test results are not immediately available, perform a rapid point-of-care test, and only start PrEP if negative 3
3. If acute HIV infection is suspected, withhold PrEP pending HIV RNA test results 3
4. Initial prescription should be limited to a 30-day supply 3
5. Subsequent prescriptions can be for 90-day supplies with appropriate monitoring 3

Monitoring Schedule

After PrEP Initiation:

• 1-month follow-up: HIV testing (combination antigen-antibody assay), adherence assessment 3, 1
• Every 3 months: HIV testing, STI screening, adherence assessment 1
• Every 6 months: Creatinine and estimated creatinine clearance testing 1
• Annually: Hepatitis C antibody testing (more frequently for high-risk individuals) 3

Special Monitoring Considerations:

• More frequent renal monitoring (every 3-6 months) for patients:
  • Over age 50
  • With baseline creatinine clearance <90 mL/min
  • With comorbidities like diabetes or hypertension 3, 1

Adherence Requirements

Adherence is crucial for PrEP efficacy 1, 5:

• MSM and transgender women: At least 4 of 7 doses per week
• Cisgender women, people who inject drugs, and heterosexual men: At least 6 of 7 doses per week

Management of PrEP in Special Situations

Recent HIV Exposure:

• If exposure occurred within 72 hours: Provide 3-drug post-exposure prophylaxis (PEP) for 1 month, then transition to 2-drug PrEP 3
• If exposure occurred >72 hours ago: Initiate standard PrEP protocol 3

Suspected Seroconversion:

• Stop PrEP immediately
• Perform confirmatory testing with HIV RNA and genotype testing
• Initiate full antiretroviral therapy if HIV infection is confirmed 3

Common Pitfalls and Caveats

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 3, 5

2. Inadequate monitoring: PrEP prescriptions should not exceed 90 days without interval HIV testing 1

3. Renal dysfunction: Monitor kidney function regularly, especially in high-risk patients. TDF/FTC is contraindicated with creatinine clearance <60 mL/min 1

4. Disparities in access: Despite increasing PrEP use (470% increase from 2014-2016), significant racial disparities exist in PrEP prescriptions, with white individuals receiving PrEP at nearly six times the rate of Black individuals despite similar risk profiles 6

5. Interruptions in PrEP delivery: Unplanned interruptions (insurance lapses, relocation) have been associated with seroconversions 3

PrEP is highly effective when used correctly, with efficacy exceeding 90% when adherence is high 5. The choice between daily oral regimens and injectable options should be based on patient-specific factors including adherence patterns, renal function, bone health, and personal preference.