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

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

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2016

Interventions

  • Other: Blood draws for tenofovir PK, renal function

Arms, Groups and Cohorts

  • Experimental: Tenofovir PK before and after SOF/LDV

Clinical Trial Outcome Measures

Primary Measures

  • Change in area under the plasma concentration (AUC) of tenofovir
    • Time Frame: 4 weeks
    • Compare tenofovir AUC0-24 before and after administration of SOF/LDV

Secondary Measures

  • Change in Estimated Glomerular Filtration Rate (eGFR)
    • Time Frame: 14 weeks
    • Compare eGFR calculated using Modification of Diet in Renal Disease (MDRD) equation before and after the addition of SOF/LDV.
  • Change in concentrations of tenofovir-diphosphate
    • Time Frame: 4 weeks
    • Compare concentrations of tenofovir-diphosphate in peripheral blood mononuclear cells and red blood cells before and after the addition of SOF/LDV

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Colorado, Denver
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jennifer Kiser, PharmD, Principal Investigator, University of Colorado, Denver

References

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