What is the best pre-exposure prophylaxis (PrEP) regimen for a patient with high-risk factors for HIV infection, including history of sexually transmitted infections (STIs) and inconsistent condom use?

Best PrEP Recommendation for High-Risk Cisgender Female

For this 28-year-old cisgender female with recurrent STIs and inconsistent condom use, the best recommendation is emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) prescribed daily (Option D).

Rationale for Daily TDF/FTC in Cisgender Women

Daily dosing of TDF/FTC is the only evidence-based regimen proven effective for cisgender women at risk of HIV through vaginal exposure 1. The critical pharmacokinetic difference is that tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 1. This makes daily dosing absolutely essential for adequate tissue protection in women 1.

• Daily TDF/FTC is recommended with the highest level of evidence (AIa) for persons at risk through sexual exposure, including heterosexual women 1
• A minimum 7-day lead-in period is required to achieve adequate tissue levels for vaginal exposures 1, 2
• After discontinuation, TDF/FTC should continue for at least 7 days after the last sexual activity for vaginal exposures 2

Why Other Options Are Incorrect

On-demand (2-1-1) dosing is NOT recommended for cisgender women 1:

• The 2-1-1 regimen is recommended ONLY for men who have sex with men (MSM) with infrequent sexual exposures 1
• Pharmacologic modeling demonstrates that less-than-daily dosing is ineffective for vaginal exposures 1
• This eliminates Options A and C

TAF/FTC (Descovy) is NOT approved or recommended for cisgender women 1, 2, 3:

• TAF/FTC is specifically indicated only for MSM and transgender women who have sex with men 3
• It is explicitly NOT recommended for prevention from receptive vaginal sex 3
• TAF/FTC is reserved for MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis 1, 3
• This eliminates Options A and B

Patient-Specific Risk Assessment

This patient meets clear criteria for PrEP initiation 1:

• Two episodes of gonorrhea in 6 months indicates high STI exposure risk 1
• Monthly sexual encounters with unknown partners (male and female) 1
• Inconsistent condom use 1
• PrEP is recommended for populations with HIV incidence above 2% per year 1

Pre-Initiation Requirements

Before prescribing TDF/FTC, obtain 1, 2:

• Combined HIV antibody and antigen testing (fourth-generation test preferred)
• Serum creatinine with calculated creatinine clearance (must be ≥60 mL/min for TDF-based PrEP) 1
• Hepatitis B surface antigen
• Hepatitis C antibody
• Pregnancy test
• Comprehensive STI screening: gonorrhea and chlamydia NAAT testing (genital and extragenital sites), syphilis serology 1

Monitoring Schedule

Quarterly follow-up is mandatory 1:

• HIV testing every 2-3 months with combined antibody/antigen assay 1
• Pregnancy testing at each visit 1
• STI screening every 3-6 months 1
• Creatinine clearance at 3 months, then every 6 months 1
• Prescriptions should not exceed 90 days without interval HIV testing 2

Critical Counseling Points

Emphasize adherence as the key determinant of efficacy 4:

• TDF/FTC efficacy exceeds 90% with consistent daily use 4
• Efficacy is highly correlated with adherence 4
• Women require strict daily dosing due to lower vaginal tissue drug concentrations 1

PrEP does not prevent other STIs 1:

• Condoms remain essential for STI prevention 1
• Her history of recurrent gonorrhea underscores this risk 1

Safety profile is favorable 4, 5:

• Only 2% discontinue due to adverse effects 4
• Common side effects (nausea, fatigue) are typically self-limited 5
• Renal and bone effects are generally reversible with discontinuation 1, 5

Pregnancy Considerations

TDF/FTC is safe during pregnancy and breastfeeding 2:

• No adverse effects have been documented in infants exposed during pregnancy 1
• This is the recommended regimen for individuals of childbearing potential 2
• Continue quarterly pregnancy testing and counsel accordingly 1