Previous failure of interferon-based therapy does not alter the frequency of HCV NS3 protease or NS5B polymerase inhibitor resistance-associated variants: longitudinal analysis in HCV/HIV co-infected patients
Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This en...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/38821 |
| Acceso en línea: | http://hdl.handle.net/11336/38821 |
| Access Level: | acceso abierto |
| Palabra clave: | Direct-Acting Antivirals Hcv Ns3 Ns5b Peg-Ifn Resistance-Associated Variants (Ravs) https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Sumario: | Since 2011, treatment of chronic hepatitis C virus (HCV) includes direct-acting antivirals (DAAs) in addition to pegylated interferon-α (peg-IFN) and ribavirin (RBV). IFN-based treatment induces strong cytotoxic T-lymphocyte activity directed to the protease- and polymerase-derived epitopes. This enhanced immunological pressure could favour the emergence of viral epitope variants able to evade immune surveillance and, when resistance-associated variants (RAVs) are implicated, could also be co-selected as a hitchhiking effect. This study analysed the dynamics of the frequency of protease and polymerase inhibitor RAVs that could affect future HCV treatment in human immunodeficiency virus (HIV) co-infected patients on stable antiretroviral therapy with previous IFN-based treatment failure. HCV genotype 1a RNA was extracted from plasma samples of 18 patients prior to and during (24 h and 4, 12, 24 and 48 weeks) therapy with peg-IFN+RBV. Next-generation sequencing was performed on HCV-RNA populations using NS3 and NS5B PCR-amplified coding regions. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima's D statistic. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (<5%), and in most cases their presence was not constant during follow-up. Only samples from two patients for each region exhibited Q80R/K/L and A421V as highly predominant variants. No significant differences were observed among sampling times for either π or D values. In conclusion, previous therapy and failure of peg-IFN+RBV were not associated with an increase in DAA-targeting NS3 or NS5B RAVs that naturally exist in HIV co-infected subjects. |
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