Adherence thresholds for emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis against HIV acquisition in cisgender women: A randomized directly observed dosing study

作者：Kenneth K. Mugwanya, M. Saina, Nelly Mugo, Samantha MaWhinney, Mary Morrow, Torin Schaafsma, Deborah Donnell, David V. Glidden, Kenneth Ngure, Clare Brown, Elena A. Rechkina, Bhavna Chohan, Linxuan Wu, Elex Hill, Eric Koome, Nina Akelo, Sarah Mbaire, Susan Morrison, Mary Kibatha, Irene Njeru, Marianne Mureithi, Corwin Coppinger, Lane R. Bushman, Jared M. Baeten, Peter L. Anderson, for the Women Benchmark Study Team · 发表于：PLoS Medicine · 年份：2025 · DOI：10.1371/journal.pmed.1004732 · 被引用次数：2 · 研究领域：HIV/AIDS Research and Interventions、HIV/AIDS drug development and treatment、HIV Research and Treatment

BACKGROUND: Oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) preexposure prophylaxis (PrEP) effectiveness against HIV acquisition highly depends on adherence. For men who have sex with men, a dosing study in the United States (US) population defined clinically meaningful tenofovir diphosphate (TFV-DP) thresholds in dried blood spots (DBS) based on the rounded 25th percentile for 2, 4, and 7 doses/week as 350, 700, and 1,250 fmol/punch. However, divergent efficacy results in the first generation randomized clinical trials of F/TDF PrEP among African women led to several hypotheses to question whether the pharmacology and adherence requirement for oral F/TDF PrEP may be different in cisgender women compared to what is already established for men. METHODS AND FINDINGS: We conducted an open-label, parallel, randomized directly observed dosing (DOD) study of oral F/TDF PrEP among women without HIV who were not pregnant or breastfeeding in Kenya. Participants were randomly assigned to 2, 4, or 7 DOD F/TDF doses/week for 8 weeks. Blood was collected weekly, and TFV-DP and emtricitabine triphosphate (FTC-TP) concentrations in DBS and peripheral blood mononuclear cells (PBMCs) were quantified using validated liquid chromatography-tandem mass spectrometry. For DBS, concentrations were quantified from a 3-mm punch using the 70% methanol/30% water (70:30) extraction method as the primary process-the same method used for the original TFV-DP benchmarks derived in US adults, and add...