title: Viral breakthrough is associated with resistance using direct acting agents in patients treated for chronic hepatitis C infection.
abstract: BACKGROUND
  Despite improved virologic response with the addition of direct acting agents to peginterferon and ribavirin treatment in chronic hepatitis C virus (HCV) genotype 1 infection, a subset of patients experience viral breakthrough while on therapy. Defining viral breakthrough and patient characteristics is important for ongoing and future HCV treatment.
  
  
  METHODS
  Thirty-four patients treated with telaprevir between June 2011 and July 2012 were retrospectively evaluated for presence of viral breakthrough. Baseline patient characteristics, time to viral breakthrough, and HCV resistance patterns were determined.
  
  
  RESULTS
  Viral breakthrough was seen in 26.5% of patients treated. Eight of 9 patients experienced breakthrough in the peginterferon and ribavirin-only phase of treatment with mean (±SD) time to breakthrough of 21.3 (±6.4) weeks. Viral breakthrough was more frequently seen in patients with genotype 1a, advanced liver fibrosis, and prior null treatment response. A majority of patients had presence of resistant mutations upon testing.
  
  
  CONCLUSIONS
  A significant proportion of patients experience viral breakthrough after completion of the direct acting agent portion of triple therapy. More frequent virologic assessments during the peginterferon and ribavirin treatment phase may be necessary to reduce cost and adverse effects of treatment.
authors.affiliation: Departments of *Medicine †Surgery, University of California, Los Angeles, CA.
authors.forename: Kali
authors.initials: K
authors.lastname: Zhou
authors.forename: Jessica
authors.initials: J
authors.lastname: Ferguson
authors.forename: Sherona
authors.initials: S
authors.lastname: Bau
authors.forename: Sammy
authors.initials: S
authors.lastname: Saab
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / 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 / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a