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Background and Aims  This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.    Methods  The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes  IL28B ,  IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4  and  ITPA  were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses.    Results  As efficacy is concerned,  IL28B  and  CTLA4  gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the  IL28B  gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was  IL28B  (OR 2.61, 95%CI 1.2–5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with  ITPA  gene polymorphism (p = 0.04). Anemia was associated with  OAS1  and  CTLA4  gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with  SOCS3  gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the  SOCS3  gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09–0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008–0.57, p = 0.01) remained significant.    Conclusions  In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with  IL28B rs8099917  polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with  SOCS3 rs4969170  polymorphism.

Pharmacogenetics of Efficacy and Safety of HCV Treatment in HCV-HIV Coinfected Patients: Significant Associations with IL28B and SOCS3 Gene Variants