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.

BACKGROUND

In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up.

METHODS

This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086.

FINDINGS

Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07-0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17-0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23-1·26]). Approximately 78-82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001).

INTERPRETATION

Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men.

FUNDING

Gilead Sciences.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests OO reports grants and personal fees from Gilead Sciences and has served on advisory boards for Gilead Sciences and ViiV Healthcare during the conduct of the study. PJR reports personal fees from Gilead Sciences and ViiV Healthcare for serving as a speaker and advisor. DP reports research grants and honoraria for advisories and conferences from Viiv Healthcare, Gilead Sciences, Janssen, and Merck, Sharp & Dohme. LCS reports grants and payment for recruitment and follow-up of participants in clinical trials, speakers' bureaus, and advisory boards from Gilead Sciences and GlaxoSmithKline during the conduct of the study. KH reports clinical research funds paid to institution from GlaxoSmithKline, ViiV Healthcare, Merck, Janssen, and Gilead Sciences during the conduct of the study. GW reports grants and personal fees from Gilead Sciences during the conduct of the study, as well as personal fees from Cepheid and Merck, Sharp & Dohme, outside the submitted work. DMA reports personal fees from Gilead Sciences and ViiV Healthcare for serving on speakers' bureaus and advisory boards, from Napo Pharmaceuticals for serving as a consultant, and from Merck for serving on speakers' bureaus. DW reports grants and personal fees from Gilead Sciences, ViiV Healthcare, and Merck, as well as personal fees from Janssen. RG reports receiving payment to his institution from Gilead Sciences for recruitment and follow-up of participants in the trial. JMB has served as a consultant for AbbVie; reports fees as a consultant, for grant or research support, as a scientific research study investigator, and for speakers' bureaus from Gilead Sciences, as well as other financial support and conference attendance sponsorship; reports other financial support and conference attendance sponsorship from Janssen; and has served as a consultant, on the speakers' bureau, and received other financial support and conference attendance sponsorship form Merck and Viiv Healthcare. CDS reports grants, personal fees, and non-financial support from Gilead Sciences, Jannsen-Cilag, GlaxoSmithKline, ViiV Healthcare, and Merck, Sharpe & Dohme, during the conduct of the study, as well as grants from AbbVie, Aperion, and Eli Lilly, personal fees from AbbVie, Aperion, Formycon, and Eli Lilly, and non-financial support from AbbVie and Aperion, outside the submitted work. YS, RE, SC, AK, CC, MD, and DMB are employees of Gilead Sciences and shareholders of Gilead Sciences stock. GK declares no competing interests.