title: Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.
abstract: Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: J
authors.initials: J
authors.lastname: Berenguer
authors.forename: D
authors.initials: D
authors.lastname: Pineda-Tenor
authors.forename: M A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: M
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: T
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.forename: A
authors.initials: A
authors.lastname: Carrero
authors.forename: C
authors.initials: C
authors.lastname: Diez
authors.forename: F
authors.initials: F
authors.lastname: Tejerina
authors.forename: S
authors.initials: S
authors.lastname: Vázquez
authors.forename: V
authors.initials: V
authors.lastname: Briz
authors.forename: S
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006239:Haplotypes; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015851:Interleukin-7 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; C508605:IL7 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015851:Interleukin-7; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a