The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients.
OBJECTIVE
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.
Ahlenstiel
Golo
G
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Nischalke
Hans Dieter
HD
Bueren
Karin
K
Berg
Thomas
T
Vogel
Martin
M
Biermer
Michael
M
Grünhage
Frank
F
Sauerbruch
Tilman
T
Rockstroh
Jürgen
J
Spengler
Ulrich
U
Nattermann
Jacob
J
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003596:Cytosine; D004359:Drug Therapy, Combination; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D013941:Thymine; D016896:Treatment Outcome
D000998:Antiviral Agents; C490611:GNB5 protein, human; D044387:GTP-Binding Protein beta Subunits; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin; D003596:Cytosine; D013941:Thymine