title: Efficacy of Direct-Acting Antiviral Combination for Patients With Hepatitis C Virus Genotype 1 Infection and Severe Renal Impairment or End-Stage Renal Disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology/Hepatology, Scripps Clinic and Scripps Translational Science Institute, La Jolla, California.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.affiliation: Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: The Liver Institute at Methodist Dallas, Dallas, Texas.
authors.forename: Parvez S
authors.initials: PS
authors.lastname: Mantry
authors.affiliation: Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Eric
authors.initials: E
authors.lastname: Cohen
authors.affiliation: Medical Associates Research Group, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Division of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Division of Gastroenterology, North Shore University Hospital, Manhasset, New York.
authors.forename: David E
authors.initials: DE
authors.lastname: Bernstein
authors.affiliation: Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Cohen
authors.affiliation: Global Pharmaceutical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Shulman
authors.affiliation: Statistics and Computer Sciences, AbbVie Inc, North Chicago, Illinois.
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Clinical Pharmacokinetics, AbbVie Inc, North Chicago, Illinois.
authors.forename: Amit
authors.initials: A
authors.lastname: Khatri
authors.affiliation: Infectious Disease Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Manal
authors.initials: M
authors.lastname: Abunimeh
authors.affiliation: Global Pharmaceutical Development, AbbVie Inc, North Chicago, Illinois.
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
authors.affiliation: Department of Gastroenterology, The Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas. Electronic address: lawitz@txliver.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
mesh_terms: D015081:2-Naphthylamine; D000368:Aged; D000813:Anilides / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates / Q000008:administration & dosage; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000821:virology; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000072230:Sustained Virologic Response; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
keywords: NS3/4A Protease Inhibitor; NS5A Inhibitor; RUBY-I; Renal Disease