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

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.

Genotype 4 Hepatitis C Virus Responds Worse than Genotype 1 to 48-Week Combination Treatment with Pegylated Interferon Alpha Plus Ribavirin: a Greek Multi-Centered Study

“…Even though IL28B has been found to be associated with SVR in some reports concerning genotype 4 as well [33][34][35], it still remains unclear whether the difference in SVR observed between endemic and European studies is related to ethnicity, HCV subtype, the mode of transmission or the IL-28B genotype [1,36]. Furthermore, distribution of IL28B polymorphisms varies between different populations worldwide and could help explain the heterogeneity in response to treatment in different ethnic or racial groups, but this still needs to be confirmed in large epidemiological studies in the Middle East and Europe.…”

HIV Co-Infections with Hepatitis B and C

“…Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) around the IL28B gene (which codes for IFN-lambda 3) which are strongly associated with treatment induced viral clearance of genotype 1 infection in HIV/HCV coinfected patients (i.e. IL28B genotype CC) [120,121]. IL28B TT/CT genotypes are associated with poorer response to IFN based treatment.…”

Interleukin 28B Polymorphisms and Hepatitis C—Translating the Association into Clinical Decision Making

“…26 These findings were also seen by Rallón et al in patients co-infected with, human immunodeficiency virus (HIV) and HCV genotype 3. 35 Moghaddam et al have shown that polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/RBV therapy in HCV genotype 3-infected patients. 36 Stattermayer et al have shown that in contrast to genotypes 1 and 4, the IL28 gene polymorphisms had no impact on SVR rates in genotype 2/3.…”

“…35,49 In patients with recurrent HCV after orthotopic liver transplantation, IL28B polymorphisms allow prediction of SVR to PEG-IFN/RBV therapy. 50,51 The value of IL28B polymorphisms have also been shown to predict response to triple therapy, including the directly acting antiviral drug telaprevir along with PEG-IFN/RBV.…”