Time to Effectiveness of Oral PrEP for Vaginally Receptive Sex
For vaginal exposures, oral TDF/FTC requires 7 days of daily dosing to achieve full protection against HIV acquisition. 1, 2, 3
Initiation Protocol
Start with a double dose of TDF/FTC on day 1, followed by single daily tablets thereafter. 1, 2, 3 This loading dose strategy helps achieve protective drug levels more rapidly in vaginal tissue, though the full 7-day period is still required for adequate protection. 1
Critical Differences by Route of Exposure
The time to protection varies significantly based on the route of potential HIV exposure:
- Vaginal exposures require 7 days of daily TDF/FTC dosing for full protection. 1, 2, 3
- Rectal exposures achieve protection within 2-3 days with adequate dosing. 1, 2, 3
This difference exists because tenofovir concentrates at substantially lower levels in vaginal tissue compared to rectal tissue, and vaginal tissue clearance is faster. 3, 4 Pharmacokinetic studies demonstrate that rectal tissue TFV and TFV-DP concentrations are 100-fold higher than concentrations in vaginal and cervical tissues. 4
Evidence Supporting the 7-Day Window
The recommendation for 7 days is based on pharmacokinetic data showing delayed drug accumulation in vaginal tissue and clinical trial evidence:
- The Partners PrEP trial demonstrated 75% efficacy for TDF/FTC in heterosexual HIV-discordant couples with high adherence (97% by pill count). 1
- The TDF2 trial showed 62% efficacy in heterosexual men and women combined with 84% adherence. 1
- Recent pooled data from 6,296 cisgender women showed that consistently high adherence (4-6 doses/week) resulted in an HIV incidence of only 0.13 per 100 person-years. 5
Common Pitfalls to Avoid
Do not use on-demand (2-1-1) PrEP for vaginal exposures. 1, 2, 3 On-demand dosing is only validated for cisgender men and others having planned receptive anal sex, not for receptive vaginal exposures. 1, 3
Do not use TAF/FTC for individuals with receptive vaginal sex as their primary exposure. 1, 2, 3, 6 TAF/FTC should be limited to cisgender men and others whose exposures do not include receptive vaginal sex, as it lacks validation for vaginal HIV prevention. 1, 3
Ensure HIV testing is completed before initiating PrEP. 1, 3, 6 A combination HIV antigen-antibody assay should be performed within 7 days before starting PrEP to exclude HIV infection. 3
Discontinuation Guidance
When stopping PrEP after vaginal exposures, continue daily dosing for at least 7 days after the last sexual activity. 1, 2, 3 This extended washout period is necessary to maintain protection as drug levels decline from vaginal tissue. 1, 3
For rectal exposures, only 2 doses after the last sexual activity are required. 1, 2
Adherence Requirements for Effectiveness
A minimum of 4 or more doses per week on average provides high-level protection against vaginal HIV acquisition. 1 In the pooled analysis of cisgender women, those with consistently daily adherence (7 doses/week) had zero HIV infections, and those with consistently high adherence (4-6 doses/week) had an incidence rate of only 0.13 per 100 person-years. 5