title: Induction pegylated interferon alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads.
abstract: OBJECTIVE
  Patients infected with hepatitis C virus (HCV) genotype 1, body weight ≥85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin.
  
  
  METHODS
  This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight ≥85 kg and HCV RNA titer ≥400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment.
  
  
  RESULTS
  Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.83-1.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.79-1.28; P = .974).
  
  
  CONCLUSIONS
  In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight ≥85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen.
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. rajender.reddy@uphs.upenn.edu
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Djamal
authors.initials: D
authors.lastname: Abdurakhmanov
authors.forename: Igor
authors.initials: I
authors.lastname: Bakulin
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Morozov
authors.forename: Giovanni Faria
authors.initials: GF
authors.lastname: Silva
authors.forename: Natalia
authors.initials: N
authors.lastname: Geyvandova
authors.forename: Carol
authors.initials: C
authors.lastname: Stanciu
authors.forename: Michael
authors.initials: M
authors.lastname: Rabbia
authors.forename: Michael
authors.initials: M
authors.lastname: McKenna
authors.forename: James A
authors.initials: JA
authors.lastname: Thommes
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000150:complications; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a