The transforming growth factor-β high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C

Background: Coinfection with the hepatitis C virus (HCV) in HIV-positive 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-β signaling has been suggested as a potential mechanism involved in HCV pathogenesis. Transforming growth factor-β, a multifunctional cytokine, displays gene polymorphisms (transforming growth factor-β codon 10T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether transforming growth factor-β gene polymorphisms affect treatment response in HCV/HIV coinfection. Methods: Transforming growth factor-β genotypes were determined in 60 HIV-positive patients with acute hepatitis C treated with pegylated interferon-α. Patients were classified into those with a high-producer genotype and others with non-high-producer genotypes. Rates of sustained virological responses were compared between high-producer and non-high-producer patients. As a control, 100 healthy, 201 HIV(+)/ HCV(ÄÌ‚'), and 148 HCV(+)/HIV(ÄÌ‚') subjects were studied. Results: Transforming growth factor-β genotype distribution did not differ significantly between the groups. In HIV/HCV coinfection carriers of the transforming growth factor-β high-producer genotype had significantly higher sustained virological response rates than patients with a transforming growth factor-β non-high-producer genotype (75 vs. 41.7%; P ≤ 0.039). In a forward-conditional stepwise regression model, transforming growth factor-β high-producer genotype was confirmed as an independent positive predictor for sustained virological response in interferon-α therapy (odds ratio, 4.4; 95% confidence interval, 1.5g-13.4; P ≤ 0.009). Conclusion: Response rates to interferon-α therapy are enhanced in acute HCV-infected HIV-positive patients carrying the transforming growth factor-β high-producerÄ€™ genotype. This finding may indicate that a transforming growth factor-β high-producerÄ€™ state can partially compensate HCV NS5A-induced inhibition of transforming growth factor-β signaling.