title: Differences in virological response to peginterferon-α plus ribavirin in HIV-positive patients coinfected with HCV subtypes 1a or 1b.
abstract: BACKGROUND
  Both viral and host factors influence response to peginterferon-α plus ribavirin (pegIFNα/RBV) in patients with chronic hepatitis C. The impact of these variables is more pronounced in HIV/Hepatitis C virus (HCV)-coinfected individuals, in whom treatment response rates are lower.
  
  
  METHODS
  Virological responses at multiple time points were assessed in all HIV/HCV-coinfected patients that completed a first course of pegIFNα/RBV. Viral responses were stratified by HCV geno/subtypes and IL28B rs12979860 variants.
  
  
  RESULTS
  A total of 331 HIV/HCV-coinfected patients were analyzed. HCV geno/subtype distribution was as follows: HCV-1a in 97, HCV-1b in 62, HCV-3 in 122, and HCV-4 in 50. Age, gender, CD4 counts, plasma HIV RNA and liver fibrosis stage did not differ significantly across HCV geno/subtypes. In contrast, mean serum HCV RNA was greater in HCV-1a compared with the rest (P < 0.0001). The proportion of IL28B CC variants was higher in HCV-3 compared with the rest (P = 0.001). Virological responses were better in HCV-1b than HCV-1a at any given time point during therapy. IL28B variants significantly influenced virological responses across all HCV-1 subtypes, with the strongest effect seen in HCV-1a. In a multivariate linear regression analysis, both HCV-1b and IL28B CC variants were significantly associated with greater HCV RNA drops at weeks 4 (R = 0.52, p < 0.0001) and 12 (R = 0.49, P < 0.0001) of therapy.
  
  
  CONCLUSIONS
  The response to pegIFNα/RBV therapy is lower in HCV-1a than HCV-1b in HIV/HCV-coinfected patients. The strongest influence of IL28B variants is seen in HCV-1a. This information may be relevant when using most directly acting antivirals in coinfected patients along with pegIFNα/RBV, given that selection of drug resistance occurs more frequently in HCV-1a than HCV-1b.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: Angela
authors.initials: A
authors.lastname: Camacho
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: Jose M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a