title: Predictors of early treatment discontinuation among patients with genotype 1 hepatitis C and implications for viral eradication.
abstract: OBJECTIVE
  A significant proportion of patients with hepatitis C virus (HCV) infection discontinue antiviral treatment prematurely. Risk factors for discontinuation before 48 weeks among patients with genotype 1 HCV vary over the course of therapy. We investigated the rates and risk factors for treatment discontinuation within 12 weeks, 12-24 weeks, and 24-48 weeks.
  
  
  METHODS
  We retrospectively evaluated data from all Veterans Affairs (VA) patients with genotype 1 HCV who initiated pegylated interferon and ribavirin therapy from 2002-2007 (n = 11,019). We accounted for appropriate discontinuation because of viral nonresponse.
  
  
  RESULTS
  Overall, 53% of patients completed at least 38.4 weeks of therapy (80% of the projected 48 weeks), 16.5% discontinued early in the setting of viral nonresponse, and 30.9% discontinued despite viral response or in the absence of virologic data. Cirrhosis, diabetes, pretreatment substance use disorder, hemoglobin, and lack of hematopoietic growth factor use independently predicted discontinuation before 12 weeks (P < .05 for all). Among patients with documented early virologic responses, higher baseline levels of creatinine, depression, and lack of growth factor use predicted discontinuation from 12-24 weeks. No factors independently predicted discontinuation from 24-48 weeks among patients responding to treatment at 24 weeks.
  
  
  CONCLUSIONS
  Early discontinuation of antiviral therapy is common. Use of growth factors was the strongest independent predictor of treatment retention before 24 weeks and should be evaluated prospectively. Early interventions may also be warranted for other risk factors for early discontinuation, such as pre-existing substance use, depression, cirrhosis, or diabetes.
authors.affiliation: Health Services Research and Development Center of Excellence, VA Puget Sound Healthcare System, Seattle, Washington, USA. Lauren.beste@va.gov
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Beste
authors.forename: George N
authors.initials: GN
authors.lastname: Ioannou
authors.forename: Meaghan S
authors.initials: MS
authors.lastname: Larson
authors.forename: Michael
authors.initials: M
authors.lastname: Chapko
authors.forename: Jason A
authors.initials: JA
authors.lastname: Dominitz
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D014766:Viremia; D016903:Drug Monitoring
chemical_list: D000998:Antiviral Agents; D036341:Intercellular Signaling Peptides and Proteins; D012254:Ribavirin; D007372:Interferons