title: Adherence to hepatitis C virus therapy and early virologic outcomes.
abstract: BACKGROUND
  Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy.
  
  
  METHODS
  We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages.
  
  
  RESULTS
  The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with > or =85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = .04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with > or =85% adherence (3.32 vs. 2.32 log IU/mL; P = .01). Early virologic response was more common among patients with > or =85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = .02) and ribavirin (73% vs. 55%; P = .08).
  
  
  CONCLUSIONS
  Adherence of > or =85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with > or =85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, 423 Guardian Dr., Philadelphia, PA 19104-6021, USA. vincentl@mail.med.upenn.edu
authors.forename: Vincent
authors.initials: V
authors.lastname: Lo Re
authors.forename: Valerianna K
authors.initials: VK
authors.lastname: Amorosa
authors.forename: A Russell
authors.initials: AR
authors.lastname: Localio
authors.forename: Rose
authors.initials: R
authors.lastname: O'Flynn
authors.forename: Valerie
authors.initials: V
authors.lastname: Teal
authors.forename: Zachariah
authors.initials: Z
authors.lastname: Dorey-Stein
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kostman
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012044:Regression Analysis; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b