F/TAF PrEP shows similar HIV incidence to F/TDF in cisgender women but noninferiority not proven

Photo by National Cancer Institute / Unsplash

Journal of acquired immune deficiency syndromes (1999) Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: McCormack Sheena, Dunn David, Kusemererwa Sylvia, Munseri Patricia, Singh Nishanta, William Wiston, … PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Interpret with caution: F/TAF did not demonstrate noninferiority to F/TDF for HIV PrEP in cisgender women due to low adherence and power.

This randomized controlled trial (RCT) evaluated the averted infections ratio (AIR) of daily oral emtricitabine/tenofovir alafenamide (F/TAF) relative to daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP) in predominantly cisgender women. The study was conducted at four sites in Uganda, Tanzania, and South Africa, enrolling 1380 participants (683 in the F/TAF group and 697 in the F/TDF group). Follow-up was 6.0 months. The primary outcome was the AIR of F/TAF relative to F/TDF, defined as the ratio of HIV incidence rates.

Results showed HIV incidence of 0.86 per 100 person-years in the F/TAF group (3 infections) and 0.56 per 100 person-years in the F/TDF group (2 infections). The AIR was 0.85 with a 90% confidence interval of 0.31 to 1.66, indicating that noninferiority of F/TAF was not statistically demonstrated. The direction of the effect was not statistically significant, and the study was underpowered to detect a difference.

Key secondary outcomes were not reported. Safety and tolerability data, including adverse events, serious adverse events, discontinuations, and tolerability, were not reported in the available information. The study's limitations include low statistical power primarily driven by low adherence. Based on week 8 dried blood spot (DBS) samples, only an estimated 14% of participants were taking 2-3 tablets per week and 9% were taking 4 or more tablets per week, indicating suboptimal adherence.

Compared to prior landmark studies, compelling evidence from multiple studies supports the efficacy of F/TAF as PrEP regardless of sex, but this study did not replicate those findings due to its limitations. The results are consistent with the known importance of adherence for PrEP effectiveness. Methodological limitations include the short follow-up duration, low adherence rates, and wide confidence intervals, which reduce certainty.

Clinically, these results do not support a switch from F/TDF to F/TAF in this population based on this study alone. The findings underscore that adherence remains a critical factor for PrEP efficacy. Questions remain about the comparative effectiveness of F/TAF versus F/TDF in populations with higher adherence, longer follow-up, and in men. Additionally, safety and tolerability data are needed to fully inform clinical decisions.

Study Details

Study typeRct

Sample sizen = 1,380

EvidenceLevel 2

Follow-up6.0 mo

PublishedJun 2026

PMID41650395

View Original Abstract ↓

BACKGROUND: F/TAF was shown to be noninferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial. SETTING: Four study sites in 3 African countries (Uganda, Tanzania, South Africa). METHODS: The 2 regimens were compared by the averted infections ratio (AIR)-the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was derived from a preceding registration cohort. Dried blood spots (DBS) were collected at regular time points for later assessment of tenofovir diphosphate levels in selected subpopulations. RESULTS: 1380 participants (697 F/TDF, 683 F/TAF) were included in the primary analysis (total follow-up 709.2 person-years); 87% were cisgender women. Three HIV infections (0.86/100 person-years) occurred in the F/TAF group versus 2 in the F/TDF group (0.56/100 person-years). The counterfactual HIV incidence was estimated to be 2.59/100 person-years (90% CI: 1.86 to 3.52), giving an AIR of 0.85 (90% CI: 0.31 to 1.66). Based on the week 8 DBS sample, only an estimated 14% of participants were classified as taking 2-3 tablets per week and 9% ≥4 tablets per week. CONCLUSIONS: Despite similar HIV incidence rates, the noninferiority of F/TAF was not demonstrated, probably because of low statistical power primarily driven by low adherence. However, there is compelling evidence from multiple studies supporting the efficacy of F/TAF as PrEP regardless of sex.