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Effects of sofosbuvir-based hepatitis C treatment on the pharmacokinetics of tenofovir in HIV/HCV-coinfected individuals receiving tenofovir disoproxil fumarate.


ABSTRACT: Background:The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions. Objectives:To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate. Methods:HIV-infected participants with acute HCV were treated for 12?weeks with sofosbuvir?+?ribavirin in Cohort 1 or 8?weeks with ledipasvir/sofosbuvir in Cohort 2 of AIDS Clinical Trials Group study 5327. Only participants taking tenofovir disoproxil fumarate were included in this analysis. Tenofovir in plasma, tenofovir diphosphate in dried blood spots and tenofovir diphosphate in PBMCs were measured pre-HCV therapy and longitudinally during the study using validated LC/MS-MS. Results:Fifteen and 22 men completed Cohorts 1 and 2, respectively. In Cohort 1, tenofovir diphosphate was 4.3-fold higher (95% CI geometric mean ratio 2.46-7.67; P?=?0.0001) in dried blood spots and 2.3-fold higher (95% CI 1.09-4.92; P?=?0.03) in PBMCs following 12?weeks of sofosbuvir?+?ribavirin versus study entry. Tenofovir in the plasma was unchanged. In Cohort 2, tenofovir diphosphate was 17.8-fold higher (95% CI 12.77-24.86; P?

SUBMITTER: MacBrayne CE 

PROVIDER: S-EPMC6054189 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Effects of sofosbuvir-based hepatitis C treatment on the pharmacokinetics of tenofovir in HIV/HCV-coinfected individuals receiving tenofovir disoproxil fumarate.

MacBrayne Christine E CE   Marks Kristen M KM   Fierer Daniel S DS   Naggie Susanna S   Chung Raymond T RT   Hughes Michael D MD   Kim Arthur Y AY   Peters Marion G MG   Brainard Diana M DM   Seifert Sharon M SM   Castillo-Mancilla Jose R JR   Bushman Lane R LR   Anderson Peter L PL   Kiser Jennifer J JJ  

The Journal of antimicrobial chemotherapy 20180801 8


<h4>Background</h4>The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions.<h4>Objectives</h4>To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate.<h4>Methods</h4>HIV-infected participants with acute HCV were treated for 12 weeks with sofosbuvir + ribavirin in Cohort 1 or 8 weeks with ledipasvir/sofosbuvir in Cohort 2 of AIDS Clinical Trials Group s  ...[more]

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