Use this link to cite:
http://hdl.handle.net/2183/26418 Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure
Loading...
Identifiers
Publication date
Authors
Chen, Qian
Perales, Celia
Soria, María Eugenia
García-Cehic, Damir
Gregori, Josep
Rodríguez-Frías, Francisco
Buti, M.
Crespo, Javier
Calleja-Panero, José Luis
Tabernero, David
Advisors
Other responsabilities
Journal Title
Bibliographic citation
Chen Q, Perales C, Soria ME, García-Cehic D, Gregori J, Rodríguez-Frías F, Buti M, Crespo J, Calleja JL, Tabernero D, Vila M, Lázaro F, Rando-Segura A, Nieto-Aponte L, Llorens-Revull M, Cortese MF, Fernandez-Alonso I, Castellote J, Niubó J, Imaz A, Xiol X, Castells L, Riveiro-Barciela M, Llaneras J, Navarro J, Vargas-Blasco V, Augustin S, Conde I, Rubín Á, Prieto M, Torras X, Margall N, Forns X, Mariño Z, Lens S, Bonacci M, Pérez-Del-Pulgar S, Londoño MC, García-Buey ML, Sanz-Cameno P, Morillas R, Martró E, Saludes V, Masnou-Ridaura H, Salmerón J, Quíles R, Carrión JA, Forné M, Rosinach M, Fernández I, García-Samaniego J, Madejón A, Castillo-Grau P, López-Núñez C, Ferri MJ, Durández R, Sáez-Royuela F, Diago M, Gimeno C, Medina R, Buenestado J, Bernet A, Turnes J, Trigo-Daporta M, Hernández-Guerra M, Delgado-Blanco M, Cañizares A, Arenas JI, Gomez-Alonso MJ, Rodríguez M, Deig E, Olivé G, Río OD, Cabezas J, Quiñones I, Roget M, Montoliu S, García-Costa J, Force L, Blanch S, Miralbés M, López-de-Goicoechea MJ, García-Flores A, Saumoy M, Casanovas T, Baliellas C, Gilabert P, Martin-Cardona A, Roca R, Barenys M, Villaverde J, Salord S, Camps B, Silvan di Yacovo M, Ocaña I, Sauleda S, Bes M, Carbonell J, Vargas-Accarino E, Ruzo SP, Guerrero-Murillo M, Von Massow G, Costafreda MI, López RM, González-Moreno L, Real Y, Acero-Fernández D, Viroles S, Pamplona X, Cairó M, Ocete MD, Macías-Sánchez JF, Estébanez A, Quer JC, Mena-de-Cea Á, Otero A, Castro-Iglesias Á, Suárez F, Vázquez Á, Vieito D, López-Calvo S, Vázquez-Rodríguez P, Martínez-Cerezo FJ, Rodríguez R, Macenlle R, Cachero A, Mereish G, Mora-Moruny C, Fábregas S, Sacristán B, Albillos A, Sánchez-Ruano JJ, Baluja-Pino R, Fernández-Fernández J, González-Portela C, García-Martin C, Sánchez-Antolín G, Andrade RJ, Simón MA, Pascasio JM, Romero-Gómez M, Antonio Del-Campo J, Domingo E, Esteban R, Esteban JI, Quer J. Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure. Antiviral Res. 2020 Feb;174:104694.
Type of academic work
Academic degree
Abstract
[Abstract]
A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients.
A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers.
Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received.
HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions.