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HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy

Guzmán-Fulgencio, Maríaa; Berenguer, Juanb; Rallón, Normac; Fernández-Rodríguez, Amandaa; Miralles, Pilarb; Soriano, Vicentec; Jiménez-Sousa, María A.a; Cosín, Jaimeb; Medrano, Joséc; García-Álvarez, Mónicaa; López, Juan C.b; Benito, José M.c; Resino, Salvadora

doi: 10.1097/QAD.0b013e32835f5b9c
Basic Science

Objectives: To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients.

Design: Retrospective follow-up study.

Methods: We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment.

Results: The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35–3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03–2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47–31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ± 0.024.

Conclusion: The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.

aUnidad de Coinfección HIV/Hepatitis, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda

bUnidad de Enfermedades Infecciosas/VIH, Hospital General Universitario ’Gregorio Marañón’

cServicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain.

Correspondence to Salvador Resino, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda–Pozuelo, Km 2.2, Majadahonda, Madrid 28220, Spain. Tel: +34 918 223 266; fax: +34 918 223 269; e-mail: sresino@isciii.es

Received 25 September, 2012

Revised 10 December, 2012

Accepted 23 January, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.