TY - JOUR
T1 - Tenofovir plasma concentration from preexposure prophylaxis at the time of potential HIV exposure
T2 - A population pharmacokinetic modeling and simulation study involving serodiscordant couples in east Africa
AU - Mallayasamy, Surulivelrajan
AU - Chaturvedula, Ayyappa
AU - Fossler, Michael J.
AU - Sale, Mark
AU - Goti, Vineet
AU - Bumpus, Namandje N.
AU - Marzinke, Mark A.
AU - Hendrix, Craig W.
AU - Haberer, Jessica E.
N1 - Funding Information:
The Partners Demonstration Project was funded by the Bill and Melinda Gates Foundation (OPP1056051), the National Institute of Mental Health of the U.S. National Institutes of Health (R01MH095507 and R01MH098744), and the U.S. Agency for International Development (AID-OAA-A-12-00023); the study was also supported by the University of Washington/Fred Hutch Center for AIDS Research (P30 AI027757) and the Johns Hopkins Center for AIDS Research (P30 AI094189), supported by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK of the National Institutes of Health.
Publisher Copyright:
© 2019 American Society for Microbiology.
PY - 2019
Y1 - 2019
N2 - The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of preexposure prophylaxis (PrEP) among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data were collected using the Medication Event Monitoring System (MEMS), and time of sexual activity was collected using the mobile phone short message 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 an a priori threshold concentrations associated with a high degree of protection from HIV infection: Plasma TFV of >40 ng/ml and peripheral blood mononuclear cell (PBMC) TFV-DP concentration of >36 fmol/million cells. The levels of coverage were 72% for TFV and 81% for TFV-DP. 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.
AB - The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of preexposure prophylaxis (PrEP) among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data were collected using the Medication Event Monitoring System (MEMS), and time of sexual activity was collected using the mobile phone short message 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 an a priori threshold concentrations associated with a high degree of protection from HIV infection: Plasma TFV of >40 ng/ml and peripheral blood mononuclear cell (PBMC) TFV-DP concentration of >36 fmol/million cells. The levels of coverage were 72% for TFV and 81% for TFV-DP. 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.
KW - Population pharmacokinetics
KW - PrEP
KW - Preexposure prophylaxis
KW - Tenofovir
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UR - http://www.scopus.com/inward/citedby.url?scp=85070658182&partnerID=8YFLogxK
U2 - 10.1128/AAC.00446-19
DO - 10.1128/AAC.00446-19
M3 - Article
C2 - 31182536
AN - SCOPUS:85070658182
SN - 0066-4804
VL - 63
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 8
M1 - e00446-19
ER -