title: HVR-1 heterogeneity during treatment with telaprevir with or without pegylated interferon alfa-2a.
abstract: BACKGROUND
  The extensive heterogeneity of the hypervariable region-1 (HVR-1) of hepatitis C virus (HCV) evidences the high genetic flexibility of HCV and was shown to be associated with virologic response to interferon-α-based therapies. However, the evolution of HVR-1 heterogeneity during treatment with directly acting antivirals has not been studied.
  
  
  METHODS
  Clonal sequence analysis of HVR-1 quasispecies in the serum of patients who were treated with telaprevir (3 × 750 mg/day) alone, telaprevir plus pegylated interferon-α-2a (pegIFN-α-2a), or pegIFN-α-2a plus placebo for 14 days was performed. HVR-1 heterogeneity, expressed as Shannon complexity and Hamming distance, was analyzed with virologic response and with the emergence of variants associated with resistance to telaprevir.
  
  
  RESULTS
  HVR-1 heterogeneity at baseline was not associated with response to telaprevir-based therapy (Shannon complexity 0.34 vs. 0.55, p = 0.38; Hamming distance 0.15 vs. 0.23, p = 0.51; for patients with or without viral breakthrough, respectively). No significant changes in HVR-1 complexity were observed from baseline to day 4 of therapy in patients in whom a continued decline in HCV RNA was observed (Shannon complexity = 0.55 vs. 0.51, p = 0.67; Hamming distance = 0.23 vs. 0.25, p = 0.81, respectively). This was similar in patients with viral breakthrough associated with telaprevir-resistant variants (Shannon complexity = 0.34 vs. 0.42, p = 0.68; Hamming distance = 0.15 vs. 0.2, p = 0.50, at baseline and day 4, respectively).
  
  
  CONCLUSIONS
  Baseline and on-treatment HVR-1 heterogeneity are not associated with early viral response to telaprevir-based therapy.
authors.affiliation: J. W. Goethe University Hospital, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Lange
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Karey
authors.forename: Tara L
authors.initials: TL
authors.lastname: Kieffer
authors.forename: Ann D
authors.initials: AD
authors.lastname: Kwong
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.forename: Henk W
authors.initials: HW
authors.lastname: Reesink
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D005260:Female; D018740:Genetic Heterogeneity / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D017423:Sequence Analysis, RNA; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C400562:HVR1 protein, Hepatitis C virus; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D011092:Polyethylene Glycols; C486464:telaprevir; C100416:peginterferon alfa-2a