Time to Full Protection for Receptive Vaginal Sex on PrEP
For a cisgender female engaging in receptive vaginal sex, full protection from HIV is achieved after 7 days of daily oral TDF/FTC (tenofovir disoproxil fumarate/emtricitabine). The answer is B) 7 days.
Rationale for 7-Day Window
The most recent 2024 International Antiviral Society-USA guidelines explicitly recommend that for vaginal, neovaginal, or "front-hole" exposures, daily dosing should be initiated with a double dose of TDF/FTC followed by single daily tablets, with dosing to continue until at least 7 days after last sexual activity. 1 This 7-day requirement reflects the pharmacokinetic reality that tenofovir concentrates at lower levels in vaginal tissue compared to rectal tissue, and clearance is faster from vaginal compartments. 2
Key Differences by Route of Exposure
The time to protection varies significantly based on the route of HIV exposure:
- For receptive vaginal sex: 7 days of daily dosing is required for full protection 1
- For receptive anal sex: Protection can be achieved more rapidly (within 2-3 days with adequate dosing), which is why on-demand 2-1-1 dosing works for men who have sex with men but is NOT validated for vaginal exposures 1, 2
Critical Clinical Considerations
Adherence is paramount for effectiveness in women. Recent pooled data from 6,296 cisgender women showed that consistently daily adherence (7 doses/week) resulted in zero HIV infections, while consistently high adherence (4-6 doses/week) resulted in only 1 infection among 658 women (incidence rate 0.13/100 person-years). 3 However, when adherence declined or was consistently low (<2 doses/week), HIV incidence increased substantially to 1.27/100 person-years. 3
The double-dose initiation strategy is now recommended. The 2024 guidelines specify starting with a double dose of TDF/FTC on day 1, followed by single daily tablets thereafter, to achieve protective drug levels more rapidly. 1
Common Pitfalls to Avoid
Do not recommend on-demand (2-1-1) dosing for this patient. On-demand PrEP is only validated for cisgender men and others having planned receptive anal sex, NOT for receptive vaginal exposures. 1, 2 Insufficient data exist to support on-demand use for vaginal exposures. 1
Do not use TAF/FTC for this patient. Daily 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, 2
Ensure HIV-negative status before initiation. A combination HIV antigen-antibody assay should be performed within 7 days before starting PrEP to exclude HIV infection. 1, 2 If acute HIV infection is suspected based on symptoms, HIV RNA testing should be added. 1
Discontinuation Guidance
When this patient decides to stop PrEP, she must continue daily dosing for at least 7 days after her last sexual activity to maintain protection during the washout period. 1 This is longer than the 2-dose requirement for rectal exposures due to slower drug accumulation and faster clearance in vaginal tissues.