AUTHOR=Pyra Maria , Anderson Pete , Haberer Jessica E. , Heffron Renee , Celum Connie , Asiimwe Stephen , Katabira Elly , Mugo Nelly R. , Bukusi Elizabeth A. , Baeten Jared M.
TITLE=Tenofovir-Diphosphate as a Marker of HIV Pre-exposure Prophylaxis Use Among East African Men and Women
JOURNAL=Frontiers in Pharmacology
VOLUME=10
YEAR=2019
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00401
DOI=10.3389/fphar.2019.00401
ISSN=1663-9812
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.