Genetic polymorphisms of IL28b gene as predictors of response to dual therapy in genotypes 1 and 4-HCV and HIV/HCV-infected patients

New Microbiol. 2015 Oct;38(4):499-509. Epub 2015 Oct 20.

Abstract

We describe the genotypes and allele distribution of interleukin 28B (IL28B) rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in hepatitis C virus (HCV) G1-4 infected patients, to assess predictive ability and to determine whether the combined determination of two IL28B SNPs might improve sustained virologic response (SVR) prediction of both in HCV mono- and HIV/HCV co-infected patients. IL28B SNPs were genotyped in 269 patients, 181 mono- and 88 co-infected, treated with pegylated interferon and ribavirin. Data stratified by HCV mono- and HCV/HIV co-infected patients showed that 58% and 31% of the rs12979860CC carriers and 49% and 21% of the rs8099917TT carriers had SVR. IL28B SNPs, HCV mono-infection and HCV RNA load were associated with SVR as independent predictors in the two study groups as a whole. ROC curve analyses in the two populations separately, based on gender, age, baseline HCV RNA load and rs12979860/rs8099917 revealed similar receiver operating characteristics (ROC) areas under the curve values. Combining the determination of IL28B SNPs, rs8099917 genotyping improved the response prediction in rs12979860CT carriers only in mono-infected patients. In the era of direct-acting antiviral agents, adopting SVR baseline predictors to orientate naïve-patient management represents an important issue. A model involving IL28B SNPs appears able to predict SVR in both populations.

Keywords: Hepatitis C virus-G1; Hepatitis C virus-G4; Human immunodeficiency virus; Interleukin-28B rs12979860; Interleukin-28B rs8099917.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Coinfection / drug therapy
  • Coinfection / genetics
  • Coinfection / virology
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • HIV-1 / physiology
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepacivirus / physiology
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Ribavirin
  • Interferons