Large global analysis finds F/TDF PrEP safe and effective, even with imperfect adherence

A large, global pooled analysis of 72 prospective studies affirmed that tenofovir disoproxil fumarate/emtricitabine (F/TDF) is effective at preventing seroconversions when taken daily and retains efficacy even when taken as little as four times per week. However, certain subgroups—particularly transgender individuals—may benefit from additional options for pre-exposure prophylaxis (PrEP) due to adherence issues.

About This Study

“HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies” was published online on March 14, 2024, in Clinical Infectious Diseases. The lead author is Raphael J. Landovitz, M.D., of the UCLA Center for Clinical AIDS Research and Education in Los Angeles, California. Several authors are from Gilead Sciences, the study drug’s manufacturer, which also supported the study.

Key Research Findings

This pooled analysis of 72 studies among 17,274 participants taking F/TDF for PrEP across the world evaluated HIV acquisition, drug resistance, adherence, and safety of F/TDF. The analysis included studies from 28 countries during 2011-2020. Median follow-up was 0.76 years, 63% of participants were cisgender men, 23% of participants were white, 33% were Black, 12% were Latinx 4% were Asian, while 29% were classified as “other/(mixed/unknown”.

HIV was newly diagnosed in 101 participants after PrEP initiation and within 60 days of PrEP discontinuation, for a rate of 0.77 seroconversions/100 person-years. Drug resistance data were available for 78 of these participants, and 28% of them had at least one mutation conferring resistance to some component of the study drug.

Tenofovir concentrations were available for 54 participants who seroconverted, with 83% of these showing <2 doses/week taken. (At least four doses per week are needed to confer good protection.) By age, 79% of ≥ 35-year-olds had sufficient adherence vs. 39% of <18-year-olds. Adherence was also greater in cisgender men (71% of that group) than cis- or transgender women (33% and 40% of these groups, respectively).

There were 0.69 adverse events/100 person-years among 4,969 participants for whom bone data were available. Among 5,172 participants with renal data, there were 11.8 adverse events/100 person-years.

Discussion Highlights and Implications for Practice

Study limitations reported included the heterogenous nature of the included studies, potential bias based on the current study’s definition of HIV incidence, some studies that included pregnant and postpartum women, inclusion of on-demand PrEP studies, and lack of longer-term follow-up data.

The authors pointed out that it is unclear whether resistance mutations were already present in the virus acquired by participants who seroconverted or were selected when F/TDF was taken for HIV prevention.

The analysis found that adherence toPrEP was consistently better in older individuals, and the researchers remarked that teens and young adults may require more support to use PrEP effectively.

Overall, the authors concluded that the current analysis confirms that F/TDF is effective in preventing seroconversions when taken daily, and that some protection remains even when it is taken less frequently.

By Barbara Jungwirth