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High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world

2019; Elsevier BV; Volume: 71; Issue: 5 Linguagem: Inglês

10.1016/j.jhep.2019.06.022

1600-0641

Ana Belén Pérez, Natalia Chueca, Miguel García Deltoro, Ana Martínez-Sapiña, María Magdalena Lara-Pérez, Silvia García‐Bujalance, Teresa Aldámiz‐Echevarría, Francisco Jesús Vera-Méndez, Juan A. Pineda, Marta Casado, J.M. Pascasio, Javier Salmerón, Juan Carlos Alados, Antonio Poyato, Francisco Téllez, Antonio Rivero‐Juárez, Dolores Merino, María Jesús Vivancos, José Miguel Rosales Zábal, Féderico García, María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto de la Iglesia, Isabel García-Arata, Miguel A. Jiménez, Fernando Jiménez, José Hernández‐Quero, Carlos Galera, Mohamed Omar Balghata, J Primo, Mar Masiá, Núria Espinosa, Marcial Delgado, Miguel Ángel Von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José Pérez de los Cobos, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María Rios, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco J. Rodríguez-Valadéz, Pedro Antequera, Cristina Delgado, Patrícia Martin, Javier Crespo, B. Becerril, Óscar Pérez, Antonio García‐Herola, J.L. Montero, Carolina Freyre, Concepción Grau,

Liver Disease Diagnosis and Treatment

Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available.GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded.A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin.In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited.Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.