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

Published

Journal Article

The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions. To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate. 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. 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 < 0.0001) in dried blood spots after 8 weeks of ledipasvir/sofosbuvir versus study entry. Tenofovir plasma concentrations were 2.1-fold higher (95% CI 1.44-2.91; P = 0.0005). Despite the increase in cellular tenofovir diphosphate concentrations, only a small decline in CLCR (6%-7%) was observed in both cohorts between study entry and end of treatment. These data indicate an unexpected drug interaction with tenofovir disoproxil fumarate and sofosbuvir at the cellular level. Additional studies are needed to determine the mechanism and clinical significance.

Full Text

Duke Authors

Cited Authors

  • MacBrayne, CE; Marks, KM; Fierer, DS; Naggie, S; Chung, RT; Hughes, MD; Kim, AY; Peters, MG; Brainard, DM; Seifert, SM; Castillo-Mancilla, JR; Bushman, LR; Anderson, PL; Kiser, JJ

Published Date

  • August 2018

Published In

Volume / Issue

  • 73 / 8

Start / End Page

  • 2112 - 2119

PubMed ID

  • 29746648

Pubmed Central ID

  • 29746648

Electronic International Standard Serial Number (EISSN)

  • 1460-2091

International Standard Serial Number (ISSN)

  • 0305-7453

Digital Object Identifier (DOI)

  • 10.1093/jac/dky146

Language

  • eng