Background:  Hepatitis C virus (HCV) co-infection is a major health problem in HIV⁺ patients. Response to HCV treatment with pegylated interferon-α (pegINF-α) ± ribavirin (RBV) is variable in this setting but might at least in part dependent on genetic host factors. The G protein b3 unit (GNB3) C825T polymorphism has been shown to affect response to treatment with interferon-α in HCV mono-infected patients. Here, we analyzed the impact of the GNB3 genotype in the context of HCV/HIV co-infection.

Methods:  We enrolled into this study 112 HIV⁺/HCV⁺ patients, receiving therapy with pegIFN-α±RBV. As a control, we analyzed 220 healthy and 98 HIV-mono-infected patients. GNB3 genotype was defined via real time polymerase chain reaction (RT-PCR) and correlated with respect to treatment response.

Results:  GNB3 genotype distribution differed significantly between HCV/HIV-co-infected patients—9TT (7.6%), 53TC (44.5%), 57CC (47.9%)) and healthy controls (32TT (14.6%), 101TC (45.9%), 87CC (39.5%) (p = 0.045, OR=1.47); and HIV mono-infected patients—20TT (20.4%), 51TC (52%), 27CC (27.6%) p = 0.003, OR=2.15).

Patients with a GNB3 CC genotype had significantly lower sustained virological response rates as compared to carriers of a  CT (52% vs 74.5%, OR 0.371, 95%CI 0.157 to 0.877; p = 0.022) or a TT genotype (75%; OR 0.361, 95%CI 0.066 to 1.964; p = 0.22). In a logistic regression analysis the GNB3 genotype was significantly associated with response to treatment (OR 2.73, 95% CI 1.18 to 6.15; p = 0.018).

Conclusions:  The GNB3 825 CC genotype is associated with poor sustained virological response rates in HIV/HCV co-infected patients. This underlines the effect of genetic host factors for treatment response.