Establishing adherence–concentration–efficacy thresholds of TDF–FTC pre-exposure prophylaxis for HIV prevention in African women: a protocol for the Women TDF–FTC Benchmark Study

作者：Linxuan Wu, M. Saina, Clare Brown, David Chege, Deborah Donnell, David V. Glidden, Kenneth Ngure, Nelly Mugo, Nina Akelo, Torin Schaafsma, Peter L. Anderson, Kenneth K. Mugwanya · 发表于：Frontiers in Reproductive Health · 年份：2024 · DOI：10.3389/frph.2024.1325257 · 被引用次数：2 · 研究领域：HIV/AIDS Research and Interventions、HIV/AIDS drug development and treatment、HIV-related health complications and treatments

Background: Oral pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a potent HIV prevention method for men and women, with its efficacy highly dependent on adherence. A pivotal HIV efficacy study combined with a directly observed pharmacological study defined the thresholds for HIV protection in men who have sex with men (MSM), which are the keys to PrEP promotion and development of new PrEP agents. For African women at risk for HIV and belonging to a priority group considered due to disproportionately high incident HIV infections, the variable adherence in PrEP clinical trials and the limited pharmacologic data have resulted in a lack of clarity about the PrEP adherence required for HIV protection. We propose a study to quantify the adherence-concentration-efficacy thresholds of TDF/FTC PrEP among African cisgender women to inform decisions about optimal PrEP dosing and adherence for HIV protection. Methods: = 15) with the primary aim of establishing benchmark concentrations in dried blood spots and peripheral blood mononuclear cells. Plasma, whole blood (WB), urine, hair, vaginal fluid, and vaginal tissue (non-pregnant women only) were archived for future testing. Drug concentrations were measured using methods validated for each biological matrix. Pharmacokinetic models were fitted to drug concentrations to quantify concentration-adherence thresholds. To define the drug concentrations associated with HIV prote...