title: Virologic characterization of genotype 4 hepatitis C virus variants in patients treated with telaprevir.
abstract: BACKGROUND
  Study C210 was a Phase IIa, exploratory trial to assess the activity of telaprevir on hepatitis C virus (HCV) early viral kinetics in treatment-naïve patients infected with genotype 4 (G4) HCV.
  
  
  METHODS
  Patients were randomized to receive peginterferon and ribavirin alone, telaprevir monotherapy (T arm), or telaprevir in combination with peginterferon/ribavirin (TPR arm) for 15 days, followed by a 46- or 48-week standard treatment phase. The current analysis aimed to characterize the genotype and phenotype of HCV G4 variants emerging during telaprevir treatment.
  
  
  RESULTS
  Five of the 8 (62.5%) patients in the telaprevir (T) arm had viral breakthrough (vBT) during the investigational treatment phase (between baseline and Day 15), compared to no patients in the TPR arm. HCV G4 viral variants with a T54A/T mutation were detected in two of these patients, as well as two other patients with detectable HCV RNA at the end of telaprevir treatment. Emergence of the T54A/T mutation was associated with a 2- to 4-fold decreased susceptibility to telaprevir. All patients with vBT during the investigational treatment phase or with a T54A/T mutation achieved undetectable HCV RNA 12 or 24 weeks after end of treatment with subsequent peginterferon/ribavirin treatment.
  
  
  CONCLUSIONS
  In this analysis in G4 HCV-infected patients, more patients in the telaprevir monotherapy arm experienced vBT with resistant variants compared to none with telaprevir combination therapy. The most commonly selected mutation T54A in telaprevir-treated G4 HCV patients was previously described in the context of G1 infection.
  
  
  BACKGROUND
  The trial was registered with ClinicalTrials.gov (NCT00580801).
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, B2340 Antwerpen, Beerse, Belgium. sdmeyer@its.jnj.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Anne
authors.initials: A
authors.lastname: Ghys
authors.forename: Inge
authors.initials: I
authors.lastname: Dierynck
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
authors.forename: Donghan
authors.initials: D
authors.lastname: Luo
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir