title: IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin.
abstract: BACKGROUND
  A single nucleotide polymorphism (SNP) upstream of the IL28B gene (rs12979860) predicts sustained virological response (SVR) to peginterferon-ribavirin therapy in chronic hepatitis C patients. There is scarce information regarding the influence of this IL28B SNP on early viral kinetics during therapy, particularly in patients coinfected with HIV, in whom treatment response is lower than in hepatitis C virus (HCV)-monoinfected patients.
  
  
  METHODS
  We selected 196 HIV/HCV-coinfected individuals who had completed a course of peginterferon-ribavirin therapy, and a validated outcome for SVR. Association of IL28B SNPs with rapid, early and end-of-treatment virological responses [rapid virological response (RVR), early virological response (EVR) and end of treatment virological response, respectively] was assessed in univariate and multivariate analyses.
  
  
  RESULTS
  Rate of SVR in the study population was 54%. Frequency of the IL28B CC genotype was 44%. The distribution of HCV genotypes was as follows: HCV-1 57%, HCV-2 1%, HCV-3 30% and HCV-4 12%. Compared to CT/TT, the CC genotype was associated with significantly higher rates of all on-treatment viral outcomes, after adjusting for other predictors of viral response as serum HCV-RNA, HCV genotype and liver fibrosis staging. IL28B CC genotype kept its predictive power of SVR in patients who did not achieve RVR or cEVR. The association between IL28B SNP and viral kinetics and treatment outcomes was significant only for HCV genotypes 1 and 4.
  
  
  CONCLUSIONS
  IL28B CC genotype is a strong predictor of virological response to therapy in HIV/HCV-coinfected patients. This effect is mediated by an increase in viral clearance during the first 12 weeks of treatment and is mainly seen in patients infected with HCV genotypes 1 and 4.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Susanna
authors.initials: S
authors.lastname: Naggie
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: John
authors.initials: J
authors.lastname: McHutchison
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a