title: IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients.
abstract: Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.
authors.affiliation: Unit of HIV/Hepatitis Coinfection, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: J
authors.initials: J
authors.lastname: Berenguer
authors.forename: N
authors.initials: N
authors.lastname: Rallón
authors.forename: M
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: J C
authors.initials: JC
authors.lastname: López
authors.forename: V
authors.initials: V
authors.lastname: Soriano
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: J
authors.initials: J
authors.lastname: Cosín
authors.forename: C
authors.initials: C
authors.lastname: Restrepo
authors.forename: M
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: P
authors.initials: P
authors.lastname: Miralles
authors.forename: J M
authors.initials: JM
authors.lastname: Benito
authors.forename: S
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018121:Receptors, Cytokine / Q000235:genetics*; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D018121:Receptors, Cytokine; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C471046:interleukin 28alpha receptor