title: Open, randomized, multicentre italian trial on PEG-IFN plus ribavirin versus PEG-IFN monotherapy for chronic hepatitis C in HIV-coinfected patients on HAART.
abstract: BACKGROUND
  Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon alpha2b (PEG-IFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response.
  
  
  METHODS
  An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEG-IFN 1.5 microg/kg/week plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 microg/kg/week (n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR).
  
  
  RESULTS
  Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50 IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A (genotype 2-3, 11/16; genotype 1-4, 4/12) and 22% in arm B (genotype 2-3, 3/15; genotype 1-4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A (genotype 2-3, 11/32; genotype 1-4, 4/37) versus 9% in arm B (genotype 2-3, 3/32; genotype 1-4, 3/34). The best predictors of SVR were the use of combination therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8. Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial prematurely due to side effects. The positive predictive value of EVR at week 8 was 65%, the negative predictive value was 86%.
  
  
  CONCLUSIONS
  PEG-IFN plus RBV can be considered a solid option for the treatment of HIV/HCV-coinfected patients. The key to successfully improving efficacy is strong compliance through strict overall patient monitoring, in order to best manage drug toxicity. EVR assessment at week 8 may become a useful stategy in the management of therapy.
authors.affiliation: II Department Infectious Diseases, Luigi Sacco Hospital, Milan, Italy. a.cargnel@hsacco.it
authors.forename: Antonietta
authors.initials: A
authors.lastname: Cargnel
authors.forename: Elena
authors.initials: E
authors.lastname: Angeli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mainini
authors.forename: Guido
authors.initials: G
authors.lastname: Gubertini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giorgi
authors.forename: Monica
authors.initials: M
authors.lastname: Schiavini
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Duca
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007558:Italy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a