August 31, 2010

Prediction of Response to Pegylated Interferon plus Ribavirin by IL28B Gene Variation in Patients Coinfected With HIV and Hepatitis C Virus

Clinical Infectious Diseases 2010;51:000–000
© 2010 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2010/5107-00XX$15.00
DOI: 10.1086/656235

MAJOR ARTICLE

Juan A. Pineda, 1 Antonio Caruz, 3 Antonio Rivero, 4 Karin Neukam, 1 Irene Salas, 3 Ángela Camacho, 4 José C. Palomares, 2 José A. Mira, 1 Antonio Martínez, 5 Carmen Roldán, 1 Julián de la Torre, 4 and Juan Macías 1

Units of 1 Infectious Diseases and 2 Microbiology, Hospital Universitario de Valme, Seville, 3 Immunogenetics Unit, Faculty of Sciences, Universidad de Jaen, Jaen, and 4 Unit of Infectious Diseases and 5 Molecular Genetics Laboratory, Unit of Clinical Analysis, Hospital Universitario Reina Sofía, Cordoba, Spain

Background. Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)–monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single‐nucleotide polymorphism rs12979860 for SVR in HIV/HCV‐coinfected patients, regardless of HCV genotype.

Methods. The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin.

Results. rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% ( ) in patients with genotype 1, 80% and 25% ( ) in patients with genotype 4, and 93% and 77% ( ) in patients with genotype 3. The median (interquartile range) low‐density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73–120 mg/dL) versus 75 mg/dL (55–91 mg/dL) ( ) in those with TC or TT. Independent predictors of SVR were HCV genotype 2–3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87–40.1; ), rs12979860 CC (OR, 5.05; 95% CI, 2.04–12.5; ), baseline plasma HCV RNA load of 600,000 IU/mL (OR, 1.99; 95% CI, 1.18–3.34; ), and female sex (OR, 4.28; 95% CI, 1.08–16.96; ).

Conclusions. IL28B gene variations independently predict SVR in HIV/HCV‐coinfected patients with HCV genotype 1 and non–genotype 1 HCV infection. The association between rs12979860 and plasma low‐density lipoprotein cholesterol suggests that the system low‐density lipoprotein ligand/receptor might be involved in the effect of this genotype.

Received 20 February 2010; accepted 9 June 2010; electronically published 30 August 2010.

Reprints or correspondence: Dr Juan A. Pineda, Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Avda de Bellavista, 41014 Sevilla, Spain (japineda@telefonica.net); or Dr Karin Neukam, Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Avda de Bellavista, 41014 Sevilla, Spain (keule165@gmail.com).
 
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