The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients

Background/Aims: Response to HCV treatment with pegylated interferon-α is variable but might at least in part depend on genetic host factors. The G protein β3 unit (GNB3) C825T polymorphism has been shown to affect treatment response in HCV mono-infection. Here, we analyzed the impact of the GNB3 genotype in the context of HCV/HIV co-infection. Methods: HIV/HCV co-infected (n = 112) and HCV mono-infected patients (n = 150), receiving therapy with pegylated IFN-α/ribavirin, were enrolled into this study. Furthermore, we analyzed 220 healthy and 92 HIV mono-infected patients. GNB3 genotype was defined and correlated with respect to treatment response. Results: GNB3 genotype distribution differed significantly between HIV/HCV co-infected patients and HIV-positive/HCV-negative (p = 0.0002) or healthy controls (p = 0.03). Patients with a GNB3 CC genotype had significantly lower SVR rates as compared to carriers of a non-CC genotype (52% versus 77%; p = 0.018). In a logistic regression analysis the GNB3 genotype and the HCV genotype were significantly associated with response to treatment (p = 0.018). In contrast to HIV/HCV co-infected patients, GNB3 genotype did not affect response to treatment in HCV mono-infected patients. Conclusions: The GNB3 825 CC genotype is associated with poor SVR rates in HIV/HCV co-infected patients. This underlines the impact of genetic host factors for treatment response.