Emtricitabine and tenofovir alafenamide (F/TAF) was found to be safe and effective in reducing the risk of HIV infection in high-risk cisgender men and transgender women who have sex with men, according to 96-week results of a phase 3 study published in The Lancet HIV that compared the treatment regimen with emtricitabine and tenofovir disoproxil fumarate (F/TDF).
In this ongoing phase 3, randomized, double-blind, active-controlled study (DISCOVER; ClinicalTrials.gov Identifier: NCT02842086) conducted at 94 clinics in North America and Europe, researchers evaluated data at 96 weeks between F/TAF (200/25 mg) and F/TDF (200/300 mg). Adult cisgender men and transgender women who have sex with men and who are at high risk of HIV acquisition were randomly assigned in a 1:1 ratio to receive F/TAF (n=2694) or F/TDF (n=2693), with matching placebo. Efficacy and safety were evaluated, including bone and renal safety.
Adherence to study drugs was high with 78% to 82% of participants reporting taking the drugs more than 95% of the time across all visits.
At 96 weeks of follow-up, 23 participants were diagnosed with HIV: 8 in F/TAF group (0.16 infections per 100 person-years; 95% CI, 0.07-0.31) and 15 in the F/TDF group (0.30 infections per 100 person-years; 95% CI, 0.17-0.49). The prespecified noninferiority margin of 1.62 was met for F/TAF as the incidence rate ratio and its 95% CI upper limit was less than 1.62 (0.54; 95% CI, 0.23-1.26).
Six safety outcomes were evaluated, including percentage change from baseline to week 96 in hip and spine bone mineral density, urine β2-microglobulin-to-creatinine ratio, retinol-binding protein-to-creatinine ratio, clinically significant elevation in urine protein-to-creatinine ratio (>22.6 mg/mmol), and change from baseline in serum creatinine. With the exception of urine protein-to-creatinine ratio, F/TAF was superior to F/TDF in all the other safety endpoints.
Drug-related adverse event rates were similar between the groups (21% in F/TAF and 24% in F/TDF), with most being grade 1 or 2 in severity. The most common adverse event not related to study drugs was a high rate of sexually transmitted infections (gonorrhea, chlamydia, and syphilis); however, the rate of infection was similar across both groups.
The researchers observed that participants taking F/TAF had significantly higher median increases in weight when compared with the F/TDF group (1.7 kg vs 0.5 kg; P <.0001).
Limitations of this study included the low number of transgender women and people from minority ethnic or racial groups. Another limitation is that people at risk for HIV through vaginal intercourse or injection drug use were excluded from this study.
Disclosure: This research was supported by Gilead Sciences. Please see the original reference for a full list of authors’ disclosures.
Ogbuagu O, Ruane PJ, Podzamczer D, et al; DISCOVER study team. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021;8(7):e397-e407. doi:10.1016/S2352-3018(21)00071-0