Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b

Abstract

BackgroundHCV subtype 1a has emerged as a predictor of poor response to triple hepatitis C therapy including boceprevir or telaprevir, which largely has been attributed to a lower resistance barrier in HCV-1a compared to -1b. ObjectivesWe examined whether a lower efficacy of pegIFN/RBV on HCV-1a than HCV-1b could alternatively contribute to explain it. Study designAll chronic hepatitis C patients who had completed a course of pegIFN/RBV therapy at our institution were examined. For this study we selected individuals that were IFN-naïve and had been successfully subtyped as 1a or 1b. Moreover, only HIV-coinfected patients were included as they represented a more uniform population in terms of demographics and treatment exposure at our institution. The IL28B rs12979860 alleles were typed using the 5′ nuclease assay. ResultsA total of 96 individuals were examined, 58 of whom harbored HCV-1a and 38 HCV-1b. IL28B allele distribution was as follows: 33 CC and 63 CT/TT. SVR was achieved by 64% of CC vs 30% of CT/TT patients (p=0.001). On the other hand, SVR was 53% in HCV-1b vs 34% in HCV-1a (p=0.08). Interestingly, the effect of IL28B variants on SVR was mainly recognized in HCV-1a (63% in CC vs 20% in CT/TT; p=0.001), being marginal on HCV-1b (64% in CC vs 46% in CT/TT; p=0.27). ConclusionsThe rate of SVR to pegIFN/RBV therapy tends to be lower in HIV-infected patients with chronic hepatitis C due to HCV-1a than HCV-1b; being the impact of IL28B variants significantly stronger on HCV-1a than HCV-1b.