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Antimicrob Agents Chemother. 2019 Jun 10. pii: AAC.00446-19. doi: 10.1128/AAC.00446-19. [Epub ahead of print]

Tenofovir plasma concentration from pre-exposure prophylaxis (PrEP) at the time of potential HIV exposure: a population pharmacokinetic modeling and simulation study involving serodiscordant couples in East Africa.

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UNT System College of Pharmacy, UNTHSC, Fort Worth, TX.
Trevena Inc, Chesterbrook, PA.
Nuventra, Raleigh, NC.
Johns Hopkins University School of Medicine, Baltimore, MD.
Massachusetts General Hospital, Boston, MA.


The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of PrEP among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data was collected using medication event monitoring system (MEMS®) and time of sexual activity was collected using mobile phone short messages service (SMS). Two plasma samples were collected at a single study visit. We integrated adherence, pharmacokinetics, and SMS data using a population pharmacokinetic (POPPK) model to simulate tenofovir plasma concentrations from PrEP at the time of sexual activity. In the first stage of this analysis, we used data from the current study to update a prior POPPK model of tenofovir (TFV) developed with data from the Partners PrEP Study (a phase III clinical trial). The second stage involved simulating plasma concentrations at the time of sexual activity using empirical Bayes estimates (EBEs) derived from the final model. In addition, EBEs from a previously published parent-metabolite model of TFV (MTN-001, an open label 3-way crossover study in healthy women) was used to simulate tenofovir-diphosphate (TFV-DP) concentrations. We estimated percent PrEP "coverage" as the number of reported sexual events during which simulated concentrations were above a priori threshold concentrations associated with a high degree of protection from HIV infection - plasma TFV >40 ng/mL and PBMC TFV-DP concentration >36 fmol/million cells. Percentage coverage was 72% for TFV and 81% for TFV-DP levels. These levels are consistent with a high degree of protection against HIV acquisition in this study of a pragmatic delivery model for antiretroviral-based HIV prevention.


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