title: Efficacy and safety of peginterferon alfa-2a/ribavirin in methadone maintenance patients: randomized comparison of direct observed therapy and self-administration.
abstract: BACKGROUND
  Adherence to chronic hepatitis C (CHC) treatment may be particularly challenging in methadone maintenance patients. We assessed the safety, tolerability, and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC.
  
  
  METHODS
  Patients were randomized 1:1 to direct observed therapy (DOT) or self-administration (SA) of peginterferon alfa-2a. DOT patients were seen weekly at methadone clinics; SA patients were seen less frequently, only at investigative sites. Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (1,000/1,200 mg/day); genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (800 mg/day).
  
  
  RESULTS
  Based on defined efficacy stopping rules, 77% (37/48) completed their targeted length of treatment, and 44% (21/48) achieved sustained virologic response (SVR). Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9, respectively, for nonsafety reasons. Over 60% and 50% of each group were >80% compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin, respectively, and over 60% with overall treatment duration. SVR rates were 54% (13/24) for DOT and 33% (8/24) for SA; 23% (3/13) and 38% (6/16), respectively, for genotype 1 and 91% (10/11) and 25% (2/8), respectively, for genotypes 2 and 3. Stepwise logistic regression analysis, showed that DOT (vs SA; OR 3.27, 95% CI 0.90-11.91, P = 0.073) and Caucasian race (vs Other; OR 13.31, 95% CI 1.42-124.71, P = 0.023) were predictors of SVR.
  
  
  CONCLUSIONS
  Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance.
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Alan D
authors.initials: AD
authors.lastname: Tice
authors.forename: Rockford G
authors.initials: RG
authors.lastname: Yapp
authors.forename: Henry C
authors.initials: HC
authors.lastname: Bodenheimer
authors.forename: Alexander
authors.initials: A
authors.lastname: Monto
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rossi
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D023801:Directly Observed Therapy; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D012646:Self Administration; D015819:Substance Abuse, Intravenous / Q000150:complications / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009294:Narcotics; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; D008691:Methadone