Effects of Sofosbuvir/Ledipasvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir

University of Colorado, Denver14 enrolled

Overview

This study evaluates the effect of sofosbuvir/ledipasvir (SOF/LDV) treatment on the pharmacokinetics (PK) and renal safety of tenofovir. Subjects receiving tenofovir-based antiretroviral therapy with human immunodeficiency virus (HIV) protease inhibitors (HIV PI/r) and initiating SOF/LDV treatment for Hepatitis C virus (HCV) will be invited to participate. The study consists of three visits: a screening visit and two abbreviated 4-hour pharmacokinetic visits (one before initiating SOF/LDV and a second approximately 4 weeks after initiating SOF/LDV).

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Hepatitis C and HIV Coinfection

Interventions

Blood draws for tenofovir PK, renal function

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * On tenofovir and a ritonavir-boosted PI for at least 30 days initiating HCV treatment with SOF/LDV * HCV RNA \<48 copies/mL at most recent clinic visit Exclusion Criteria: * eGFR \< 60 ml/min * history of renal disease * Pregnant or planning pregnancy * Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes

Outcomes

Primary Outcomes

Change in area under the plasma concentration (AUC) of tenofovir

Compare tenofovir AUC0-24 before and after administration of SOF/LDV

Time frame: 4 weeks

Secondary Outcomes

Change in Estimated Glomerular Filtration Rate (eGFR)

Compare eGFR calculated using Modification of Diet in Renal Disease (MDRD) equation before and after the addition of SOF/LDV.

Time frame: 14 weeks

Change in concentrations of tenofovir-diphosphate

Compare concentrations of tenofovir-diphosphate in peripheral blood mononuclear cells and red blood cells before and after the addition of SOF/LDV