On-Demand PrEP Options Beyond Daily Truvada
Yes, on-demand (2-1-1) dosing with TDF/emtricitabine (Truvada) is the only validated alternative to daily PrEP, but it is restricted to cisgender men and transgender women having planned receptive anal sex—it is not recommended for women, people who inject drugs, or anyone with receptive vaginal exposures. 1, 2
The 2-1-1 Dosing Regimen
On-demand PrEP follows a specific schedule: 2
- 2 doses taken 2-24 hours before sex (ideally closer to 24 hours than 2 hours for optimal protection) 1
- 1 dose taken 24 hours after the first dose 2
- 1 dose taken 24 hours after the second dose 2
This regimen demonstrated 86% risk reduction in the IPERGAY study among MSM. 2
Critical Population Restrictions
Who Can Use On-Demand PrEP:
- Cisgender men having infrequent planned receptive anal sex 1, 2
- Transgender women having planned receptive anal sex 2
Who Cannot Use On-Demand PrEP:
- Women (cisgender or transgender) with any vaginal exposure risk—tenofovir concentrates 10-fold lower in vaginal tissue than rectal tissue and clears faster, requiring daily dosing for 7 days to achieve protection 1, 2, 3
- People who inject drugs—only daily TDF/FTC is validated for this population 1, 2
- Individuals with active hepatitis B infection (HBsAg positive)—intermittent dosing risks acute hepatitis flares and hepatic decompensation, particularly with cirrhosis 1, 2
Why TAF/Emtricitabine (Descovy) Is Not an Option
TAF/emtricitabine is NOT validated for on-demand dosing and should not be used for this purpose. 2 Additionally:
- TAF/FTC should be limited to cisgender men whose exposures do not include receptive vaginal sex or injection drug use 2
- On-demand dosing has only been validated with TDF/FTC, not TAF/FTC 2
Real-World Experience
A French cohort study of 1,049 PrEP users found that 75.6% of predominantly MSM participants opted for on-demand PrEP, with an HIV incidence of only 0.82/100 person-years (all four infections occurred in poorly adherent patients). 4 This demonstrates real-world effectiveness when adherence is maintained.
Common Pitfalls to Avoid
- Never prescribe on-demand PrEP for women—the pharmacokinetics in vaginal tissue do not support intermittent dosing 2, 3
- Do not use TAF/FTC for on-demand dosing—no validation exists for this formulation 2
- Screen for hepatitis B before initiating any PrEP regimen—intermittent TDF exposure in HBV-positive patients is contraindicated 1, 2
- Ensure HIV testing with combination antigen-antibody assay before starting—mandatory to exclude acute HIV infection 1, 2
Monitoring Requirements
Even with on-demand PrEP: 1, 2
- HIV testing every 3 months (mandatory)
- STI screening every 3 months
- PrEP prescriptions should not exceed 90 days without interval HIV testing
- Creatinine monitoring at least every 6 months (TDF-based PrEP contraindicated if creatinine clearance <60 mL/min/1.73m²)