Background:  Co-infection with the hepatitis C virus (HCV) in HIV⁺ patients is an emerging health problem. The factors affecting response to HCV-specific therapy are poorly understood but may involve host genetic factors. HCV NS5A-induced inhibition of transforming growth factor (TGF) -β signaling has been suggested as a potential mechanism involved in HCV pathogenesis. TGF-β, a multifunctional cytokine, displays gene polymorphisms (TGF-β codon 10 T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether TGF-β gene polymorphisms affect the treatment response in HCV/HIV co-infection.

Methods:  TGF-b genotypes were determined in 60 HIV⁺ patients with acute hepatitis C treated with pegylated interferon-alpha (pegIFN-α). Patients were classified as those with a high-producer genotype vs all other genotypes. Rates of sustained virological responses were compared between high-producer and non- high-producer patients. As a control, 100 healthy, 210 HIV⁺/HCV^–, and 148 HCV⁺/HIV^– subjects were studied.

Results:  TGF-b genotype distribution did not differ significantly between the groups. In HIV/HCV-co-infection carriers of the TGF-β high-producer genotype had significantly higher sustained virological response rates than patients with a TGF-β non- high-producer genotype (75% vs 41.7%; p = 0.039). In a forward-conditional stepwise regression model TGF-b high-producer genotype was confirmed as an independent positive predictor for sustained virological response in pegIFN-α therapy (OR 4.4, 95%CI 1.5 to 13.4; p = 0.009).

Conclusions:  Response rates to pegIFN-α therapy are enhanced in acute HCV/HIV-co-infected patients carrying the TGF-β high-producer genotype. This finding may indicate that a TGF-b high-producer state can partially compensate HCV NS5A-induced inhibition of TGF-b signaling.