title: IL28B alleles exert an additive dose effect when applied to HCV-HIV coinfected persons undergoing peginterferon and ribavirin therapy.
abstract: BACKGROUND
  Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score.
  
  
  METHODS
  We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score.
  
  
  RESULTS
  231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7-5.3] and 3.4 [1.7-6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR.
  
  
  CONCLUSIONS
  IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores.
authors: Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Barham K Abu
authors: BK
authors: Dayyeh
authors: Namrata
authors: N
authors: Gupta
authors: Kenneth E
authors: KE
authors: Sherman
authors: Paul I W
authors: PI
authors: de Bakker
authors: Raymond T
authors: RT
authors: Chung
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; 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