Paper # 165LB
Strong Association of a Single Nucleotide Polymorphism Located Near the Interleukin-28b Gene with Response to Hepatitis C Therapy in HIV/HCV Co-infected Patients
Norma Rallon*1, S Naggie2, J Benito1, J Medrano1, C Restrepo1, D Goldstein3, K Shianna3, J McHutchison2, and V Soriano1
1Hosp Carlos III, Madrid, Spain; 2Duke Clin Res Inst, Durham, NC, US; and 3Inst for Genome Sci and Policy, Durham, NC, US
Background: Response to hepatitis C therapy is lower
for HIV/HIV co-infected than HCV-monoinfected patients. Given that current HCV
therapy is poorly tolerated, there is interest in the identification of better predictors
of treatment response. A SNP located near the IL28b gene (rs12979860), which
codes for IFN-λ, has recently been found to predict treatment response in
HCV-monoinfected patients with HCV genotype 1. There is no information in
HIV/HCV co-infected individuals and/or other HCV genotypes.
Methods: From a cohort of 650 HIV/HCV co-infected
patients receiving care at a single clinic in Madrid, Spain, we included 198 patients completing therapy with pegylated interferon-ribavirin with
validated outcomes (106 SVR versus 92 non-responders; overall SVR 46%) who had
informed written consent for DNA testing. The SNP near the IL28b gene,
rs12979860, was examined using the 5’ nuclease assay with allele specific
TaqMan probes. Genotyping was conducted in a blinded fashion. Bivariate (chi-square
test) and multivariate (logistic regression) analyses were used to determine
predictors of treatment outcome.
Results: In this study, 164 patients were included
in the IL28b genotyping final analysis; 34 patients had inadequate sample for
analysis. HCV genotype distribution included: HCV-1 58%, HCV-3 31%, and HCV-4 11%.
The SVR rate was significantly higher in patients with the CC alleles than in
those with CT/TT alleles across all HCV genotypes (Table 1). In the
multivariate analysis, the rs12979860 CC genotype was a strong predictor of SVR
(OR = 3.4; 95%CI 1.4 to 7.9; P =0.006), independent of other
well-known predictors such as HCV genotype 3 (OR = 8.1; 3.0 to 21.7; P <0.0001),
baseline serum HCV-RNA <600,000 IU/mL (OR = 13.9; 3.9 to 48.1; P <0.001)
and fibrosis < F3-F4 (OR = 3.4; 1.3 to 9.2; P =0.016).
Table 1: SVR rate by prevalence of polymorphism
Conclusions: The rs12979860 SNP located near the IL28b
gene is strongly associated with SVR in HIV/HCV co-infected patients. The
impact is recognized across all HCV genotypes. These findings suggest that
IL28b genotyping may play a critical role in the medical management of this
difficult-to-treat population.
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