RT Journal Article
T1 Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure.
A1 Chen, Qian
A1 Perales, Celia
A1 Soria, María Eugenia
A1 García-Cehic, Damir
A1 Gregori, Josep
A1 Rodríguez-Frías, Francisco
A1 Buti, María
A1 Crespo, Javier
A1 Calleja, José Luis
A1 Tabernero, David
A1 Vila, Marta
A1 Lázaro, Fernando
A1 Rando-Segura, Ariadna
A1 Nieto-Aponte, Leonardo
A1 Llorens-Revull, Meritxell
A1 Cortese, Maria Francesca
A1 Fernandez-Alonso, Irati
A1 Castellote, José
A1 Niubó, Jordi
A1 Imaz, Arkaitz
A1 Xiol, Xavier
A1 Castells, Lluís
A1 Riveiro-Barciela, Mar
A1 Llaneras, Jordi
A1 Navarro, Jordi
A1 Vargas-Blasco, Víctor
A1 Augustin, Salvador
A1 Conde, Isabel
A1 Rubín, Ángel
A1 Prieto, Martín
A1 Torras, Xavier
A1 Margall, Nuria
A1 Forns, Xavier
A1 Mariño, Zoe
A1 Lens, Sabela
A1 Bonacci, Martin
A1 Pérez-Del-Pulgar, Sofía
A1 Londoño, Maria Carlota
A1 García-Buey, María Luisa
A1 Sanz-Cameno, Paloma
A1 Morillas, Rosa
A1 Martró, Elisa
A1 Saludes, Verónica
A1 Masnou-Ridaura, Helena
A1 Salmerón, Javier
A1 Quíles, Rosa
A1 Carrión, José Antonio
A1 Forné, Montserrat
A1 Rosinach, Mercè
A1 Fernández, Inmaculada
A1 García-Samaniego, Javier
A1 Madejón, Antonio
A1 Castillo-Grau, Pilar
A1 López-Núñez, Carme
A1 Ferri, María José
A1 Durández, Rosa
A1 Sáez-Royuela, Federico
A1 Diago, Moisés
A1 Gimeno, Concepción
A1 Medina, Rafael
A1 Buenestado, Juan
A1 Bernet, Albert
A1 Turnes, Juan
A1 Trigo-Daporta, Matilde
A1 Hernández-Guerra, Manuel
A1 Delgado-Blanco, Manuel
A1 Cañizares, Angelina
A1 Arenas, Juan Ignacio
A1 Gomez-Alonso, Maria Juana
A1 Rodríguez, Manuel
A1 Deig, Elisabet
A1 Olivé, Gemma
A1 Río, Oscar Del
A1 Cabezas, Joaquín
A1 Quiñones, Ildefonso
A1 Roget, Mercè
A1 Montoliu, Silvia
A1 García-Costa, Juan
A1 Force, Lluís
A1 Blanch, Silvia
A1 Miralbés, Miguel
A1 López-de-Goicoechea, María José
A1 García-Flores, Angels
A1 Saumoy, María
A1 Casanovas, Teresa
A1 Baliellas, Carme
A1 Gilabert, Pau
A1 Martin-Cardona, Albert
A1 Roca, Rosa
A1 Barenys, Mercè
A1 Villaverde, Joana
A1 Salord, Silvia
A1 Camps, Blau
A1 Silvan di Yacovo, María
A1 Ocaña, Imma
A1 Sauleda, Silvia
A1 Bes, Marta
A1 Carbonell, Judit
A1 Vargas-Accarino, Elena
A1 Ruzo, Sofía P
A1 Guerrero-Murillo, Mercedes
A1 Von Massow, Georg
A1 Costafreda, María Isabel
A1 López, Rosa Maria
A1 González-Moreno, Leticia
A1 Real, Yolanda
A1 Acero-Fernández, Doroteo
A1 Viroles, Silvia
A1 Pamplona, Xavier
A1 Cairó, Mireia
A1 Ocete, María Dolores
A1 Macías-Sánchez, José Francisco
A1 Estébanez, Angel
A1 Quer, Joan Carles
A1 Mena-de-Cea, Álvaro
A1 Otero, Alejandra
A1 Castro-Iglesias, Ángeles
A1 Suárez, Francisco
A1 Vázquez, Ángeles
A1 Vieito, David
A1 López-Calvo, Soledad
A1 Vázquez-Rodríguez, Pilar
A1 Martínez-Cerezo, Francisco José
A1 Rodríguez, Raúl
A1 Macenlle, Ramiro
A1 Cachero, Alba
A1 Mereish, Gasshan
A1 Mora-Moruny, Carme
A1 Fábregas, Silvia
A1 Sacristán, Begoña
A1 Albillos, Agustín
A1 Sánchez-Ruano, Juan José
A1 Baluja-Pino, Raquel
A1 Fernández-Fernández, Javier
A1 González-Portela, Carlos
A1 García-Martin, Carmen
A1 Sánchez-Antolín, Gloria
A1 Andrade, Raúl Jesús
A1 Simón, Miguel Angel
A1 Pascasio, Juan Manuel
A1 Romero-Gómez, Manolo
A1 Antonio Del-Campo, José
A1 Domingo, Esteban
A1 Esteban, Rafael
A1 Esteban, Juan Ignacio
A1 Quer, Josep
K1 Antiviral treatment
K1 Direct-acting antivirals
K1 Failure
K1 HCV
K1 NGS
K1 RAS
AB 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.
YR 2019
FD 2019-12-16
LK http://hdl.handle.net/10668/14850
UL http://hdl.handle.net/10668/14850
LA en
DS RISalud
RD Apr 7, 2025