What is the recommended PrEP (Pre-Exposure Prophylaxis) regimen for individuals at high risk of HIV exposure?

HIV Pre-Exposure Prophylaxis (PrEP) Regimen

The recommended first-line PrEP regimen for individuals at high risk of HIV exposure is tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg taken once daily, with proven efficacy exceeding 90% when adherence is maintained. 1, 2, 3

Primary Regimen Selection

• TDF/FTC 300mg/200mg once daily remains the gold standard across all populations and exposure routes, with the strongest evidence rating 2, 4, 5
• This regimen is effective for men who have sex with men (MSM), heterosexual men and women, transgender individuals, people who inject drugs, and serodiscordant couples 1, 2, 3
• Efficacy exceeds 90% with maintained adherence but drops to 44% with suboptimal adherence, making adherence counseling critical 3, 5

Population-Specific Dosing Strategies

For Men Who Have Sex With Men (MSM):

• Initiate with a double dose (2 tablets) on day 1, then continue once daily to achieve maximal protection within 24 hours 1, 2, 3
• Alternative on-demand "2-1-1" dosing is acceptable for MSM only: 2 tablets taken 2-24 hours before sex, 1 tablet 24 hours later, and 1 tablet 48 hours after the first dose 1, 2, 3
• When stopping PrEP, continue for 2 days after the last at-risk exposure 3

For Cisgender Women and Transgender Women:

• Daily dosing is mandatory—on-demand dosing is NOT recommended for vaginal exposure 2, 3
• Maximum protection requires approximately 7 days of daily dosing 3
• When stopping PrEP, continue for 7 days after the last at-risk exposure 3
• Daily dosing is critical because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 3

For All Other Populations:

• Take once daily without loading dose 3
• Maximum protection requires approximately 7 days of daily dosing 3

Alternative Regimen: TAF/FTC

• For MSM with creatinine clearance 30-60 mL/min, osteopenia, or osteoporosis, use tenofovir alafenamide/emtricitabine (TAF/FTC) instead of TDF/FTC 1, 3, 6
• Do NOT use TAF/FTC as first-line for cisgender women, as insufficient efficacy data exists for vaginal exposure 2

Pre-Initiation Testing Requirements

Before prescribing PrEP, obtain the following tests 1, 2, 3:

• Combined HIV antibody and antigen testing (with HIV RNA testing if acute infection is suspected)
• Serum creatinine with calculated creatinine clearance
• Hepatitis B surface antigen (HBsAg)
• Hepatitis C antibody
• Hepatitis A antibody (for MSM and people who inject drugs)
• Nucleic acid amplification testing for gonorrhea and chlamydia (genital and non-genital sites)
• Syphilis testing
• Pregnancy test for individuals of childbearing potential

Monitoring Schedule During PrEP Use

At 1 Month After Initiation:

• Combined HIV antibody and antigen test 1, 3

Every 3 Months (Quarterly):

• HIV antibody/antigen testing 1, 2, 3
• STI screening (gonorrhea, chlamydia, syphilis) 1, 2, 3
• Pregnancy testing for individuals of childbearing potential 2, 3
• Adherence assessment 2

Renal Function Monitoring:

• At 3 months after initiation, then every 6 months 1, 2
• More frequent monitoring (every 3 months) if baseline creatinine clearance <90 mL/min, diabetes, hypertension, or age >50 years 2, 3

Special Populations

Pregnancy and Breastfeeding:

• TDF/FTC is safe during pregnancy and breastfeeding with no documented adverse fetal effects and should be continued 2, 3

Hepatitis B Co-infection:

• For HBsAg-positive individuals, if PrEP is discontinued, consider indefinite continuation or transition to hepatitis B treatment with close monitoring for hepatitis flares using ALT/AST testing 2, 3

Critical Pitfalls to Avoid

• Do NOT prescribe PrEP without confirming HIV-negative status, as resistance can develop if prescribed during acute HIV infection 2, 5
• Do NOT use on-demand (2-1-1) dosing for cisgender women or transgender women—daily dosing is mandatory for vaginal exposure 2, 3
• Do NOT use TAF/FTC as first-line for cisgender women due to insufficient efficacy data for vaginal exposure 2
• Do NOT forget the 7-day lead-in period for women, as protection is not immediate 2
• Counsel that PrEP does not prevent other STIs—condoms remain essential for comprehensive STI prevention 2, 3
• Only 2% of people discontinue PrEP due to adverse effects, primarily kidney and gastrointestinal issues 4, 5

Transitioning from PEP to PrEP

• An immediate transition from nonoccupational post-exposure prophylaxis (nPEP) to PrEP is beneficial for persons with anticipated repeat or ongoing potential HIV exposures, including HIV testing at the completion of the nPEP regimen with a prompt transition to a recommended PrEP regimen 7