The Safety and Efficacy of a PrEP Regimen With TAF Versus Traditional TDF in HIV Prevention

Emtricitabine/tenofovir disoproxil fumarate (F/TDF), the only US-approved drug for HIV preexposure prophylaxis (PrEP), has been shown to safely prevent HIV when used daily. A group of investigators sought to explore whether emtricitabine plus tenofovir alafenamide (TAF)—the prodrug formulation of the nucleotide reverse-transcriptase inhibitor tenofovir—also is safe and effective as daily HIV PrEP.

Compared with TDF, TAF has higher intracellular tenofovir levels, lower plasma tenofovir levels, and improved renal and bone safety when used to treat HIV. Previous research has shown that TAF has a more favorable safety profile than the traditional TDF formulation and is efficacious at lower doses than TDF.

In the DISCOVER study, Charles B. (Brad) Hare, MD, at the University of California, San Francisco, and Kaiser Permanente San Francisco Medical Center, and colleagues described the efficacy and safety of F/TAF compared with the traditional regimen of F/TDF for PrEP in 5387 cisgender men who have sex with men (MSM) and transgender women (TGW) in North America and Europe who were at high risk of acquiring HIV.

Dr. Hare discussed the study results of earlier this week at the Conference on Retroviruses and Opportunistic Infections (CROI) 2019 in Seattle, Washington.

In the randomized, double-blind, active-controlled study, participants at high risk for HIV acquisition received either F/TAF (200/25 mg) or F/TDF (200/300 mg) daily. The primary endpoint was the rate of HIV infection per 100 person-years when 50% of the participants completed 96 weeks of PrEP.

Of the 5387 adult participants at 94 sites in 11 countries (60% in the United States), the mean age was 36 (range, 18-76 years), 9% were black, 1% were TGW, 23% had prior PrEP use, and 41% had more than 3 receptive condomless anal sex partners in the 90 days before enrollment.

Across the F/TAF and F/TDF arms, 21 participants acquired HIV during the study period—a significantly lower infection rate than would be expected among those at risk but not taking PrEP in the United States. Both daily regimens were relatively well-tolerated during the almost 2-year follow-up period, with a low incidence of adverse events and low discontinuation rates.

“The DISCOVER study, with 5387 participants and 8756 person-years of follow-up, demonstrates that F/TAF is noninferior to F/TDF in preventing HIV infection in MSM and trans-women at high risk,” Dr Hare concluded.

For more information about this study, click here.

For more CROI 2019 coverage, click here.

—Michael Gerchufsky

Reference:

Hare CB, Coll J, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI) 2019; March 4-7, 2019; Seattle, WA. http://www.croiconference.org/sessions/phase-3-discover-study-daily-ftaf-or-ftdf-hiv-preexposure-prophylaxis. Accessed March 7, 2019.