title: Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.
abstract: BACKGROUND
  Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.
  
  
  RESULTS
  Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.
  
  
  CONCLUSIONS
  Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00553930.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain. lflopez@telefonica.net
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Luis
authors.initials: L
authors.lastname: Jimenez-Jimenez
authors.forename: María F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Rosario
authors.initials: R
authors.lastname: Mata
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.forename: Manuel
authors.initials: M
authors.lastname: Marquez-Solero
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use; D012449:Safety; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a