| Abstract |
The equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in ribavirin cellular uptake. Polymorphisms at the ENT1 gene may influence ribavirin activity as part of hepatitis C virus (HCV) therapy. A retrospective study was conducted in 109 human immunodeficiency virus (HIV)-infected patients who were infected with HCV genotypes 1 or 4 who had received pegylated interferon (pegIFN)-ribavirin. Single nucleotide polymorphisms (SNPs) at the ENT1 gene were examined using TaqMan 5 -nuclease assays. In the study population, allelic frequencies at rs760370 were as follows: A3 (43 [39\%] of 109 patients), AG (50 [46\%] of 109 patients), and GG (16 [15\%] of 109 patients). Achievement of rapid virological response was more frequent in GG carriers than in AA/AG carriers (50\% vs 17\%, respectively; Pp. 007). In multivariate analysis, the GG genotype (odds ratio [OR], 15.9; 95\% confidence interval [CI], 2.8-92.2; P <.002), a baseline serum HCV-RNA level < 600,000 IU/mL (OR, 45.7; 95\% CI, 8.7-240.5; P <.001) and a serum ribavirin trough concentration > 2.5 mu g/mL (OR, 4.8; 95\% CI, 1.3-17.1; P <.016) were associated with rapid virological response. When 2 or more of these factors were present, positive and negative predictive values of rapid virological response were 65\% and 91\%, respectively. In summary, a SNP rs760370A -> G at the ENT1 gene influences the chance of rapid virological response to pegIFN-ribavirin therapy in HIV-infected patients with chronic HCV infection due to HCV genotypes 1 or 4, most likely modulating intracellular ribavirin exposure within hepatocytes. |
