title: Sustained virological response after 14-day treatment with danoprevir and 48-week treatment with pegylated interferon-α2a (40 KD) plus ribavirin.
abstract: BACKGROUND
  Danoprevir (RG7227) is an inhibitor of the HCV NS3/4A protease. In two Phase Ib studies of treatment-naive patients with chronic HCV genotype 1 infection, danoprevir administration for 14 days was associated with HCV RNA median reduction reaching 3.8 log(10) in monotherapy and 5.7 log(10) in combination therapy with pegylated interferon (PEG-IFN)-α2a (40 KD) plus ribavirin (RBV). After the protocol-defined phase, patients were free to continue with PEG-IFN/RBV. Sustained virological response (SVR) was evaluated in patients who continued treatment with PEG-IFN/RBV.
  
  
  METHODS
  Retrospective analysis of the patients who received a 14-day monotherapy regimen with danoprevir (100 or 200 mg every 8 or 12 h), or 14-day triple therapy with danoprevir (100, 200 or 300 mg every 8 h, or 400, 600 or 900 mg every 12 h) with PEG-IFN-α2a (40 KD; 180 μg/week subcutaneously) and RBV (1,000-1,200 mg/day) followed by PEG-IFN-α2a (40 KD; 180 μg/week subcutaneously) and RBV (1,000-1,200 mg/day) for 46 weeks (triple therapy group) for a total of 48 weeks (monotherapy group).
  
  
  RESULTS
  Data were collected from 15 patients with danoprevir monotherapy and 24 patients with danoprevir-based triple therapy. Virological results are expressed using an intention-to-treat principle. Premature treatment discontinuation occurred in five patients. Rapid virological response (RVR; week 4) rate was 50% and 69.6% and SVR rate was 60% and 70.8% in the monotherapy and triple therapy groups, respectively. RVR was highly predictive of SVR (>90%; HCV RNA<15 IU/ml).
  
  
  CONCLUSIONS
  The addition of danoprevir for 14 days to PEG-IFN/RBV treatment results in a high SVR rate in HCV genotype 1 treatment-naive patients.
authors.affiliation: Liver Unit and CIC-IRB1040, Saint Eloi Hospital, Montpellier, France. dom-larrey@chu-montpellier.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Christophe
authors.initials: C
authors.lastname: Carenco
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boyer
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.forename: Regine
authors.initials: R
authors.lastname: Rouzier
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D054833:Isoindoles; D007769:Lactams / Q000008:administration & dosage* / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D016898:Interferon-alpha; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; C553752:danoprevir; D011392:Proline; C100416:peginterferon alfa-2a