Efficacy of Direct-Acting Antiviral Combination for Patients With Hepatitis C Virus Genotype 1 Infection and Severe Renal Impairment or End-Stage Renal Disease

Gastroenterology. 2016 Jun;150(7):1590-1598. doi: 10.1053/j.gastro.2016.02.078. Epub 2016 Mar 11.

Abstract

Background & aims: Although hepatitis C virus (HCV) infection is common in patients with end-stage renal disease, highly efficacious, well-tolerated, direct-acting antiviral regimens have not been extensively studied in this population. We investigated the safety and efficacy of ombitasvir co-formulated with paritaprevir and ritonavir, administered with dasabuvir (with or without ribavirin) in a prospective study of patients with stage 4 or 5 chronic kidney disease (CKD).

Methods: We performed a single-arm, multicenter study of treatment-naïve adults with HCV genotype 1 infection, without cirrhosis and with CKD stage 4 (estimated glomerular filtration rate, 15-30 mL/min/1.73 m(2)) or stage 5 (estimated glomerular filtration rate, <15 mL/min/1.73 m(2) or requiring hemodialysis). Twenty patients were given ombitasvir co-formulated with paritaprevir and ritonavir, administered with dasabuvir for 12 weeks. Patients with HCV genotype 1a infections also received ribavirin (n = 13), whereas those with genotype 1b infection did not (n = 7). The primary end point was sustained virologic response (serum HCV RNA <25 IU/mL) 12 weeks after treatment ended (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities.

Results: All 20 patients completed 12 weeks of treatment. Eighteen of the 20 patients achieved SVR12 (90%; 95% confidence interval: 69.9-97.2). One patient death after the end of the treatment (unrelated to the treatment) and 1 relapse accounted for the 2 non-SVRs. Adverse events were primarily mild or moderate, and no patient discontinued treatment due to an AE. Four patients experienced serious AEs; all were considered unrelated to treatment. Ribavirin therapy was interrupted in 9 patients due to anemia; 4 received erythropoietin. No blood transfusions were performed.

Conclusions: In a clinical trial, the combination of ombitasvir, paritaprevir, and ritonavir, administered with dasabuvir, led to an SVR12 in 90% of patients with HCV genotype 1 infection and stage 4 or 5 CKD. The regimen is well tolerated, though RBV use may require a reduction or interruption to manage anemia. ClinicalTrials.gov ID NCT02207088.

Keywords: NS3/4A Protease Inhibitor; NS5A Inhibitor; RUBY-I; Renal Disease.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Anilides / administration & dosage
  • Antiviral Agents / administration & dosage*
  • Carbamates / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / virology
  • Macrocyclic Compounds / administration & dosage
  • Male
  • Middle Aged
  • Prospective Studies
  • Ribavirin / administration & dosage
  • Ritonavir / administration & dosage
  • Sulfonamides / administration & dosage
  • Sustained Virologic Response
  • Uracil / administration & dosage
  • Uracil / analogs & derivatives

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Macrocyclic Compounds
  • Sulfonamides
  • ombitasvir
  • Ribavirin
  • Uracil
  • dasabuvir
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT02207088