Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/17450
Title
Analysis of IL28B alleles with virologic response patterns and plasma cytokine levels in HIV/HCV-coinfected patients
Author(s)
Fernandez-Rodriguez, Amanda ISCIII | Rallón, Norma | Berenguer, Juan | Jimenez-Sousa, Maria Angeles ISCIII | Cosín, Jaime | Guzman-Fulgencio, Maria ISCIII | Restrepo, Clara | Lopez, Juan C | Garcia-Alvarez, Monica ISCIII | Miralles, Pilar | Soriano, Vicente | Benito, Jose M | Resino, Salvador ISCIII
Date issued
2013-01-14
Citation
AIDS. 2013 Jan 14;27(2):163-73.
Language
Inglés
Document type
research article
Abstract
Objectives: To estimate the impact of interleukin 28B (IL28B) polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) and their haplotypes on hepatitis C virus (HCV) treatment (peg-interferon-α and ribavirin) success in 324 HIV/HCV-coinfected patients. We also explore the behavior of plasma cytokine levels. Design: Retrospective follow-up study. Methods: Virologic response to HCV treatment was measured by plasma HCV viral load at different endpoints: rapid virologic response (RVR), early virologic response (EVR), end-of-treatment virologic response (ETVR) and sustained virologic response (SVR). IL28B polymorphisms were genotyped using GoldenGate assay. Finally, 13 cytokines were measured at baseline in 57 plasma samples using a multiplex immunoassay kit. Results: IL28B polymorphisms were strongly associated to virologic responses (RVR, EVR, ETVR, and SVR), although only for HCV genotypes 1 and 4 (P < 0.05). Strong linkage disequilibrium was detected for rs12980275/rs11881222 (r = 0.94) and rs8099917/rs7248668 (r = 0.99). IL28B haplotypes showed association but no improvement on treatment outcome prediction. Thus, the genotyping of only one single-nucleotide polymorphism was enough for predicting treatment response in GT1/4 patients with favorable rs12980275 (AA) genotype, while for subjects harboring unfavorable genotypes, the inclusion of rs8099917 was useful (SVR increased from 31 to 45%). Moreover, patients with rs12980275 (AA) that achieved SVR showed reduced plasma levels of Th1 (IFN-γ), Th2 (IL-6 and IL-9), and proinflammatory (TNF-α) cytokines. Conclusion: The presence of IL28B polymorphisms was significantly associated with HCV clearance during and after HCV therapy. The evaluated cytokine profile was much more favorable in patients with rs12980275 (AA) who achieved SVR.
Subject
AIDS | Chronic hepatitis C | Cytokine | Interleukin 28B | Liver | Single-nucleotide polymorphisms | Therapy
MESH
Adult | Alleles | Antiviral Agents | Coinfection | Cytokines | Drug Therapy, Combination | Female | Follow-Up Studies | HIV Infections | Hepacivirus | Hepatitis C, Chronic | Humans | Interferon alpha-2 | Interferon-alpha | Interferons | Interleukins | Logistic Models | Male | Middle Aged | Polyethylene Glycols | Polymorphism, Single Nucleotide | Recombinant Proteins | Retrospective Studies | Ribavirin | Viral Load
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