@article{a4743f2021ae413db496662d28634a79,
title = "Tenofovir-diphosphate as a marker of HIV pre-exposure prophylaxis use among east african men and women",
abstract = "Background: Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. Therefore, we evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP. Methods: Participants were enrolled as members of HIV serodiscordant couples as part of an open-label PrEP study in Kenya and Uganda. Blood samples were taken at quarterly visits and stored as DBS, which were analyzed for TFV-DP concentrations. Results: Among 150 samples from 103 participants, MEMs data indicated that 87 (58%) took ≥4 doses and 62 (41%) took ≥6 per week consistently over the 4 weeks prior to sample collection. Sensitivities of DBS TFV-DP levels were 62% for the ≥4 doses/week category (≥700 fmol/punch TFV-DP) and 44% for the ≥6 doses/week category (≥1050 fmol/punch TFV-DP); specificities were 86 and 94%, respectively. There were no statistically significant differences in these sensitivities and specificities by gender. Conclusion: In this sample of East African PrEP users, categories of TFV-DP concentrations developed from directly observed PrEP use among United States populations had high specificity but lower than expected sensitivity. Sensitivity was lowest when MEMS data indicated high adherence (i.e., ≥6 doses/week). PrEP studies and implementation programs should carefully consider the sensitivity and specificity of the TFV-DP levels used for adherence feedback.",
keywords = "Adherence, Africa, HIV, Pre-exposure prophylaxis, Tenofovir-diphosphate, Women",
author = "{Partners Demonstration Project Study Team} and Maria Pyra and Pete Anderson and Haberer, {Jessica E.} and Renee Heffron and Connie Celum and Stephen Asiimwe and Elly Katabira and Mugo, {Nelly R.} and Bukusi, {Elizabeth A.} and Baeten, {Jared M.} and Deborah Donnell and Ruanne Barnabas and Jessica Haberer and Harald Haugen and Craig Hendrix and Lara Kidoguchi and Mark Marzinke and Susan Morrison and Jennifer Morton and Norma Ware and Monique Wyatt and {Edna Tindimwebwa}, {S. A.} and {Nulu Bulya}, {E. K.} and Elizabeth Bukusi and Josephine Odoyo and Mugo, {Nelly Rwamba} and Kenneth Ngure",
note = "Funding Information: The Partners Demonstration Project was funded by the National Institute of Mental Health of the United States National Institutes of Health (R01 MH095507), the Bill & Melinda Gates Foundation (OPP1056051), and the United States Agency for International Development (AID-OAA-A-12-00023). Research reported in this publication was supported by the UW/Fred Hutch Center for AIDS Research, funded by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK of the National Institutes of Health under award number P30 A1027757 and the HIV Prevention Trials Network (UM1 AI068613). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, NIH, or the United States Government. Funding Information: The Partners Demonstration Project was funded by the National Institute of Mental Health of the United States National Institutes of Health (R01 MH095507), the Bill & Melinda Gates Foundation (OPP1056051), and the United States Agency for International Development (AID-OAA-A-12-00023). Research reported in this publication was supported by the UW/Fred Hutch Center for AIDS Research, funded by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK of the National Institutes of Health under award number P30 A1027757 and the HIV Prevention Trials Network (UM1 AI068613). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, NIH, or the United States Government. We thank the couples who participated in this study and the members of the Colorado Antiviral Pharmacology Laboratory. Publisher Copyright: {\textcopyright} 2019 Pyra, Anderson, Haberer, Heffron, Celum, Asiimwe, Katabira, Mugo, Bukusi and Baeten. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
doi = "10.3389/fphar.2019.00401",
language = "English (US)",
volume = "10",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S. A.",
number = "APR",
}