TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients

Abstract

BackgroundToll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. ObjectivesTo analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients. Study designWe performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate® assay with VeraCode®. The outcome variables were early virologic response (EVR) and sustained virologic response (SVR). ResultsIn a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR=0.20; p=0.018) and SVR (aOR=0.38; p=0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p=0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p=0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p=0.030), whereas GG haplotype increased the likelihood (p=0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p=0.019, p=0.043 and p=0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p=0.039). ConclusionsOur study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.