Pharmacogenetics of Efficacy and Safety of HCV Treatment in HCV-HIV Coinfected Patients: Significant Associations with IL28B and SOCS3 Gene Variants
Background and Aims: This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFN alpha) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV co...
| Autores: | , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2012 |
| País: | España |
| Recursos: | Conselleria de Salut i Consum del Govern de les Illes Balears |
| Repositorio: | Docusalut |
| Idioma: | inglés |
| OAI Identifier: | oai:docusalut.com:20.500.13003/12978 |
| Acesso em linha: | https://hdl.handle.net/20.500.13003/12978 |
| Access Level: | acceso abierto |
| Palavra-chave: | Genotype Male Models, Genetic Adult Suppressor of Cytokine Signaling Proteins Interferon-alpha Models, Statistical Female Suppressor of Cytokine Signaling 3 Protein HIV Infections Phenotype Ribavirin Polymorphism, Genetic Genetic Variation Pharmacogenetics Gene Expression Regulation, Viral Interleukins Humans Hepatitis C Interferón-alfa Modelos Estadísticos Proteínas Supresoras de la Señalización de Citocinas Variación Genética Regulación Viral de la Expresión Génica Femenino Infecciones por VIH Masculino Modelos Genéticos Interleucinas Humanos Genotipo Farmacogenética Fenotipo Proteína 3 Supresora de la Señalización de Citocinas Adulto Polimorfismo Genético Ribavirina |
| Resumo: | Background and Aims: This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFN alpha) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods: The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNF alpha, IFN gamma, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results: As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95% CI 0.008-0.57, p = 0.01) remained significant. Conclusions: In HCV-HIV coinfected patients treated with PegIFN alpha and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism. |
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