Starting Dose for PrEP
For all populations at risk of HIV acquisition, initiate tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg once daily as the standard first-line regimen. 1, 2, 3
Population-Specific Initiation Strategies
Men Who Have Sex with Men (MSM)
Start with a loading dose of 2 tablets (600mg/400mg) on day 1, then continue with 1 tablet (300mg/200mg) once daily thereafter. 1, 2 This loading dose achieves maximal protection within 24 hours of the double dose ingestion. 1
For MSM with infrequent sexual exposures, the alternative "2-1-1" on-demand dosing is acceptable: 2 tablets taken 2-24 hours before sex, 1 tablet 24 hours after the first dose, and 1 final tablet 24 hours later. 1 This event-driven approach reduced HIV risk by 86% in the IPERGAY trial. 1
Continue daily dosing for 2 days after the last at-risk exposure when stopping or interrupting PrEP. 1
Cisgender Women, Transgender Women, and Other Populations
Start with the standard single tablet dose (300mg/200mg) once daily—do NOT use a loading dose. 1, 2 Maximum protection requires approximately 7 days of daily dosing before full efficacy is achieved. 1, 2
Daily dosing is mandatory for cisgender women and transgender women because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, and clearance is faster. 1, 4 The on-demand "2-1-1" dosing is NOT recommended for vaginal exposure. 2, 3
Continue daily dosing for 7 days after the last at-risk exposure when stopping or interrupting PrEP. 1
For people who inject drugs, use the same standard daily dosing regimen (300mg/200mg once daily). 1
Alternative Regimen: TAF/FTC
Tenofovir alafenamide/emtricitabine (TAF/FTC) should be considered ONLY for MSM with creatinine clearance 30-60 mL/min who have osteopenia, osteoporosis, or are at high risk for these complications. 1, 3
TAF/FTC lacks efficacy data for receptive vaginal sex and should NOT be used as first-line for cisgender women. 2, 3
Pre-Initiation Requirements
Before prescribing the first dose, obtain the following tests:
Combined HIV antibody and antigen testing within 7 days before initiation to exclude HIV infection. 1, 2 An HIV RNA assay may be needed to exclude acute HIV infection in high-risk populations. 1
Serum creatinine with calculated creatinine clearance (TDF-based PrEP is contraindicated when creatinine clearance falls below 60 mL/min/1.73 m²). 1, 3, 5
Hepatitis B surface antigen (HBsAg) and hepatitis C antibody. 1, 2, 3
STI screening (gonorrhea, chlamydia, syphilis) via nucleic acid amplification testing. 1, 2, 4
Pregnancy test for individuals of childbearing potential. 2, 3, 4
Common Pitfalls to Avoid
Do not extrapolate the loading dose strategy to non-MSM populations. The double-dose initiation is only validated for MSM due to the rapid drug concentration achieved in rectal tissue. 1 Women require the full 7-day lead-in period with daily dosing. 1, 2
Do not use TAF/FTC for women or people who inject drugs. TAF/FTC has never been studied for HIV prevention in these populations, and no efficacy data exist for vaginal or injection-related exposures. 2, 3
Do not prescribe PrEP without confirming HIV-negative status. Using TDF/FTC alone in someone with undiagnosed HIV infection risks development of drug resistance. 1, 2
Do not forget that PrEP does not prevent other sexually transmitted infections. Condoms remain recommended for all genital penetrative sex acts. 1
Special Populations
Pregnancy and breastfeeding: Continue daily TDF/FTC (300mg/200mg once daily) as it is safe with no documented adverse fetal effects. 1, 2, 3
Adolescents ≥15 years and ≥35 kg: Use the same adult dosing (300mg/200mg once daily). 2, 3
HBsAg-positive individuals: Consider indefinite continuation or transition to hepatitis B treatment if stopping PrEP, as discontinuation can cause severe hepatitis flares. 2, 3, 5