Genetic Variation Predicts Poor Treatment Response in HIV-HCV Coinfected Patients  

By Liz Highleyman

Response to anti-HCV therapy depends on a variety of factors. Along with viral load and genotype, demographic characteristics such as age and sex also predict treatment response. And, according to a study presented at the 42nd Annual Meeting of the European Association for the Study of the Liver this month in Barcelona, host genetic factors also appear to play a role.

As background, researchers noted that the G protein B3 unit (GNB3) C825T polymorphism has been shown to affect treatment response in HCV monoinfected patients. In this study, they analyzed the effect of GNB3 genotype in HIV-HCV coinfected individuals.

The study enrolled 150 HCV monoinfected subjects and 112 HIV-HCV coinfected patients receiving treatment with pegylated interferon plus ribavirin. The investigators also analyzed 98 HIV monoinfected individuals and 220 healthy volunteers with neither virus.

Results

• GNB3 genotype distribution differed significantly between HIV-HCV coinfected patients and both HIV positive individuals without HCV and uninfected controls subjects.
  
  
• Among patients with HCV genotype 1, 69% of HCV monoinfected patients achieved an end-of-treatment response (ETR) and 47% achieved sustained virological response (SVR).
  
  
• Among HIV-HCV coinfected patients, the ETR rate was 76.8% and the SVR rate was 63.8%.
  
  
• Response rates were markedly lower among patients with a HCV genotypes 1 or 4, as compared to those with genotypes 2 or 3 (ETR 72% vs. 90%; SVR 58% vs. 79%).
  
  
• As expected, patients with HCV genotypes 2 or 3 were significantly more likely to achieve SVR compared to those with genotype 1 (79% vs 58%, respectively).
  
  
• Among HIV-HCV coinfected patients, those with the GNB3 CC genotype had significantly lower SVR rates compared with carriers of a non-CC genotype (52% vs 77%).
  
  
• In a logistic regression analysis, GNB3 genotype and HCV genotype were significantly associated with response to treatment in coinfected subjects.
  
  
• However, GNB3 genotype did not affect treatment response in HCV mononfected patients.

Conclusion

“The GNB3 825 CC genotype is associated with poor SVR rates in HIV-HCV coinfected patients,” the authors concluded. “This underlines the impact of genetic host factors for treatment response.”

An unexplained finding of this study is the lower ETR and SVR rates observed among HCV monoinfected compared with HIV-HCV coinfected patients, since most other studies have found that coinfected individuals respond more poorly to interferon-based therapy.

Department of Internal Medicine I, University Of Bonn, Germany; Medizinische Klinik Mit Schwerpunkt Hepatologie und Gastroenterologie, Universitaetsklinikum Charité, Campus-Virchow-Klinikum, Universitätsmedizin Berlin, Germany.

04/27/07

Reference
J Nattermann, K Bueren, HD Nischalke, and others. The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients. 42nd Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain. April 11-15, 2007.

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