Article
Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods
Antimicrobial Agents and Chemotherapy
(2016)
Abstract
Antiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners (the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information (PRDI) from 404 subjects (corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects (corresponding to 327 drug concentration records) in an ancillary adherence study. Model development was conducted with NONMEM (7.2), using PRDI with a steady-state assumption or using PRDI replaced with electronic monitoring records where available. A two-compartment model with first-order absorption was the best model in both modeling approaches, with the need for an absorption lag time when electronic monitoring-based dosing records were included in the analysis. Age, body weight, and creatinine clearance were significant covariates on clearance, but only creatinine clearance was retained in the final models per stepwise selection. Sex was not a significant covariate on clearance. Tenofovir population pharmacokinetic parameter estimates and the precisions of the parameters from the two final models were comparable with the point estimates of the parameters, differing from 0% to 35%, and bootstrap confidence intervals widely overlapped. These findings indicate that PRDI was sufficient for population pharmacokinetic model development in this study, with a high level of adherence per multiple measures.
Keywords
- Antiretroviral therapy,
- HIV infections -- Treatment,
- Population pharmacokinetics,
- Tenofovir,
- Serodiscordant couples
Disciplines
Publication Date
September, 2016
DOI
10.1128/AAC.00559-16
Publisher Statement
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Citation Information
Lu Y, Goti V, Chaturvedula A, Haberer JE, Fossler MJ, Sale ME, Bangsberg D, Baeten JM, Celum CL, Hendrix CW. 2016. Population pharmacokinetics of tenofovir in HIV-1-uninfected members of serodiscordant couples and effect of dose reporting methods. Antimicrob Agents Chemother 60:5379–5386. doi:10.1128/AAC.00559-16.