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Interferon-stimulated genes are associated with peginterferon/ribavirin treatment response regardless of IL28B alleles in hepatitis C virus/HIV-coinfected patients

Rallon, Norma I.a,*; Lopez-Fernandez, Luis A.b,*; Garcia, Maria Isabelb; Benguria, Albertoc; Fiorante, Silvanad; Soriano, Vincenta; Benito, José M.a

doi: 10.1097/QAD.0b013e32835ce2c1
Basic Science

Background: The interaction between interferon-stimulated genes (ISGs) expression, IL28B genotypes and hepatitis C treatment outcomes has been mainly evaluated in the liver tissue from hepatitis C virus (HCV)-monoinfected patients but with controversial results. Herein, we examined whether more easily accessible peripheral blood mononuclear cells (PBMCs) could be used for this purpose in HIV–HCV coinfected patients, a population in whom HCV-induced liver disease progression occurs more rapidly and treatment response is lower.

Methods: Gene expression profiles were examined using the human whole genome Agilent microarray platform in PBMCs collected from HIV/HCV-coinfected patients who had completed a course of peginterferon/ribavirin therapy with validated outcomes. Patients were split out according to the achievement of sustained virological response (SVR) and IL28B rs12979860 genotypes. The GeneSpringGX software was used to select genes differentially expressed in the different groups.

Results: Nineteen HIV/HCV-coinfected individuals receiving antiretroviral therapy and having undetectable plasma HIV-RNA were examined. Global gene expression profiles showed 42 genes differentially expressed according to treatment outcome and 56 according to IL28B genotype. Common genes were not found and functions differed for genes belonging to either group. Whereas at least 26 out of 37 repressed genes (70.3%) in SVR patients were ISGs, none of the 56 differentially expressed genes in carriers of distinct IL28B variants were ISGs (P < 0.0001).

Conclusion: Baseline expression of ISGs in PBMCs from HCV/HIV-coinfected patients influence the response to peginterferon/ribavirin therapy, regardless of IL28B genotypes. PBMC specimens can reliably be used for evaluating ISGs expression in clinical practice.

aInfectious Diseases Department, Hospital Carlos III

bPharmacogenetic Laboratory, Hospital Gregorio Marañón

cGenomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC)

dEuropean University, Madrid, Spain.

*Norma I. Rallon and Luis A. Lopez-Fernandez contributed equally to the writing of this article.

Correspondence to Dr Norma I. Rallón, Infectious Diseases Department, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain. Tel: +34 91 4532500; fax: +34 91 7336614; e-mail: normaibon@yahoo.com

Received 18 June, 2012

Revised 25 October, 2012

Accepted 21 November, 2012

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© 2013 Lippincott Williams & Wilkins, Inc.