On-Demand TAF for HIV PrEP is Not Recommended
On-demand tenofovir alafenamide (TAF) is not recommended for HIV pre-exposure prophylaxis (PrEP) as there is insufficient evidence supporting its efficacy compared to tenofovir disoproxil fumarate (TDF). 1
Current PrEP Recommendations
- TDF/emtricitabine (TDF/FTC) remains the recommended PrEP agent for all populations at risk of HIV through sexual exposure or injection drug use 1
- Daily oral TAF/FTC use should be limited to cisgender men and others whose exposures do not include receptive vaginal sex (including neovaginal sex) or injection drug use alone 1
- On-demand (2-1-1) dosing has only been validated with TDF/FTC, not with TAF/FTC 1
On-Demand PrEP Evidence
- On-demand TDF/FTC (2-1-1 dosing) is effective for HIV prevention among MSM with an 86% risk reduction in the IPERGAY study 1
- The 2-1-1 dosing schedule consists of:
- 2 doses of TDF/FTC taken 2-24 hours before sex
- 1 dose 24 hours after the first dose
- 1 dose 24 hours after the second dose 1
- The ANRS PREVENIR study showed that on-demand TDF/FTC was as effective as daily TDF/FTC in MSM with HIV incidence of 1.1 cases per 1000 person-years in both groups 2
Why TAF is Not Recommended for On-Demand PrEP
- The 2024 International Antiviral Society-USA panel guidelines do not recommend TAF for on-demand PrEP 1
- Earlier guidelines from 2018 explicitly stated that "TDF/lamivudine, TAF/emtricitabine, or TDF alone are not recommended for PrEP" 1
- TAF has different pharmacokinetics than TDF, with potentially insufficient tissue concentrations when used in an on-demand fashion 3
- No clinical trials have evaluated the efficacy of on-demand TAF/FTC for HIV prevention 1
Population-Specific Considerations
- For women, daily TDF/FTC is especially important as tenofovir concentrates at 10-fold lower levels in vaginal tissue than in rectal tissue and clearance is faster 4, 1
- On-demand PrEP is only recommended for cisgender men and transgender women having planned receptive anal sex 1
- For people who inject drugs, daily TDF/FTC is the only recommended regimen 1
Safety Considerations
- While TAF/FTC has improved bone and renal safety profiles compared to TDF/FTC for daily use 3, these benefits have not been established for on-demand dosing
- TDF-based PrEP is not recommended for persons with creatinine clearance below 60 mL/min/1.73 m² 1
- For individuals with active HBV infection, on-demand PrEP with either TDF or TAF is not recommended due to risk of hepatitis flare and hepatic decompensation 1
Clinical Monitoring
- HIV testing with a combination antigen-antibody assay is mandatory before initiating any PrEP regimen 1
- Follow-up visits every 3 months are recommended for HIV testing and STI screening 1
- PrEP prescriptions should not exceed 90 days without interval testing for HIV infection 1
Conclusion
For patients seeking on-demand PrEP, TDF/FTC using the 2-1-1 dosing strategy is the only recommended option, particularly for MSM with infrequent sexual exposures. TAF/FTC should only be used as a daily PrEP option for cisgender men and transgender women who have sex with men, not as an on-demand regimen.