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

J Hepatol. 2007 Sep;47(3):348-55. doi: 10.1016/j.jhep.2007.04.008. Epub 2007 May 24.

Abstract

Background/aims: Response to HCV treatment with pegylated interferon-alpha is variable but might at least in part depend on genetic host factors. The G protein beta3 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-alpha/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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Cytosine
  • Drug Therapy, Combination
  • Female
  • GTP-Binding Protein beta Subunits / genetics*
  • Genotype
  • HIV Infections / complications*
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Recombinant Proteins
  • Ribavirin / therapeutic use
  • Thymine
  • Treatment Outcome

Substances

  • Antiviral Agents
  • GNB5 protein, human
  • GTP-Binding Protein beta Subunits
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Ribavirin
  • Cytosine
  • Thymine