title: TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients.
abstract: BACKGROUND
  Toll-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.
  
  
  OBJECTIVE
  To 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.
  
  
  METHODS
  We 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).
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. Electronic address: majimenezsousa@yahoo.es.
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.affiliation: IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Rallón
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.affiliation: Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Cosín
authors.affiliation: IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Retana
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Miralles
authors.affiliation: IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Benito
authors.affiliation: Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. Electronic address: sresino@isciii.es.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy / Q000821:virology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006239:Haplotypes; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D051196:Toll-Like Receptor 3 / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D012254:Ribavirin
keywords: Chronic hepatitis C; HCV therapy; HIV; Interferon; Polymorphisms