title: Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection.
abstract: Alisporivir is a cyclophilin inhibitor with pan-genotypic anti-hepatitis C virus (HCV) activity and a high barrier to viral resistance. The VITAL-1 study assessed alisporivir as interferon (IFN)-free therapy in treatment-naïve patients infected with HCV genotype 2 or 3. Three hundred forty patients without cirrhosis were randomized to: arm 1, alisporivir (ALV) 1,000 mg once-daily (QD); arm 2, ALV 600 mg QD and ribavirin (RBV); arm 3, ALV 800 mg QD and RBV; arm 4, ALV 600 mg QD and pegylated IFN (Peg-IFN); or arm 5, Peg-IFN and RBV. Patients receiving IFN-free ALV regimens who achieved rapid virological response (RVR) continued the same treatment throughout, whereas those with detectable HCV RNA at week 4 received ALV, RBV, and Peg-IFN from weeks 6 to 24. Overall, 300 patients received ALV-based regimens. In arm 1 to arm 4, the intent-to-treat rates of sustained virological response (SVR) 24 weeks after treatment (SVR24) were from 80% to 85%, compared with 58% (n = 23 of 40) with Peg-IFN/RBV. Per-protocol analysis showed higher SVR24 rates in patients who received ALV/RBV, IFN-free after RVR (92%; n = 56 of 61) than with ALV alone after RVR (72%; n = 13 of 18) or with Peg-IFN/RBV (70%; n = 23 of 33). Both RVRs and SVRs to ALV IFN-free regimens were numerically higher in genotype 3- than in genotype 2-infected patients. Viral breakthrough was infrequent (3%; n = 7 of 258). IFN-free ALV treatment showed markedly better safety/tolerability than IFN-containing regimens.
  
  
  CONCLUSIONS
  ALV plus RBV represents an effective IFN-free option for a proportion of patients with HCV genotype 2 or 3 infections, with high SVR rates for patients with early viral clearance. Further investigations of ALV in IFN-free combination regimens with direct-acting antiviral drugs deserve exploration in future trials.
authors.affiliation: National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.|INSERM U955, Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: Medical University of Bialystok, Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
authors.affiliation: Klinikum der Albert-Ludwigs-Universität, Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rasenack
authors.affiliation: Prince of Songkla University, Songklanagarind Hospital, Hat-Yai, Songkhla, Thailand.
authors.forename: Teerha
authors.initials: T
authors.lastname: Piratvisuth
authors.affiliation: Kaohsiung Medical University, Chang-Ho Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Bart's and The London School of Medicine, Queen Mary's University of London, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Global Hospitals, Mumbai, India.
authors.forename: Samir
authors.initials: S
authors.lastname: Shah
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: INSERM U955, Créteil, France.|Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.affiliation: Beijing Novartis Pharma Co Ltd, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Novartis Institute of Biomedical Research, Emeryville, CA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Wong
authors.affiliation: Novartis Institute of Biomedical Research, Cambridge, MA.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Avila
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; C100416:peginterferon alfa-2a; C499715:alisporivir