Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients

AIDS. 2010 May 15;24(8):F23-9. doi: 10.1097/QAD.0b013e3283391d6d.

Abstract

Background: Given that peginterferon-ribavirin treatment is poorly tolerated, there is interest in the identification of predictors of response, particularly in HIV/hepatitis C virus (HCV)-coinfected patients that respond less than HCV-monoinfected individuals. A single nucleotide polymorphism (SNP) near the IL28B gene (rs12979860) has been shown to predict treatment response in HCV-monoinfected patients carrying genotype 1. Information is lacking for HIV/HCV-coinfected individuals and/or other HCV genotypes.

Methods: From 650 HIV/HCV-coinfected patients, we identified those who had completed a course of peginterferon-ribavirin therapy with a validated outcome and available repository DNA. The rs12979860 SNP was examined in a blinded fashion.

Results: A total of 164 patients were included in the final IL28B genotyping analysis, 90 (55%) of whom achieved sustained virological response (SVR). HCV genotype distribution was as follows: HCV-1 58%, HCV-3 31% and HCV-4 11%. Overall, the SVR rate was higher in patients with CC than in those CT/TT genotypes: 56 of 75 (75%) versus 34 of 89 (38%) (P < 0.0001). The effect of the SNP was seen in HCV genotypes 1 and 4 but not in HCV genotype 3 carriers. In the multivariable analysis (odds ratio; 95% confidence interval; P value), the rs12979860 CC genotype was a strong predictor of SVR (3.7; 1.6-8.5; 0.002), independent of HCV genotype 3 (8.0; 3.1-21.0; <0.001), serum HCV-RNA less than 600,000 IU/ml (11.9; 3.8-37.4; <0.001) and lack of advanced liver fibrosis (3.5; 1.4-8.9; 0.009).

Conclusion: The rs12979860 SNP located near the IL28B gene is associated with HCV treatment response in HIV-infected patients with chronic hepatitis C due to genotypes 1 or 4. Thus, IL28B genotyping should be considered as part of the treatment decision algorithm in this difficult-to-treat population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • Hepacivirus / genetics*
  • Hepatitis C / complications
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide / genetics
  • RNA, Viral
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • Risk Factors
  • Spain
  • Treatment Outcome

Substances

  • IFNL3 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a