1. High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world
- Author
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Ana María Martínez-Sapiña, Concepción Grau, Maria Rios, Javier Crespo, Óscar Pérez, Elisa Fernández, Antonio Rivero-Juárez, Carlos Mínguez, Juan Carlos Alados-Arboledas, Miguel Jimenez, Joaquín Primo, Antonio Poyato, Juan Manuel Pascasio, Mónica Vélez, Natalia Chueca, Juan Arenas, Javier Salmerón, Berta Becerril, José Luis Montero, María Dolores Ocete, Clotilde Fernández, Marta Casado, Sergi Reus, Teresa Aldámiz-Echevarría, Carolina Freyre, Pedro Antequera, María Jesús Vivancos-Gallego, Carmen Hidalgo, Miguel Angel Simón, Cristina Delgado, Alberto de la Iglesia, Dolores Merino, Enrique Bernal, Mar Masiá, José Hernández-Quero, Daniel Navarro, Nuria Espinosa, Carlos Galera, Federico García, Ana Belén Pérez, Antonio Aguilera, Jesús Santos, Patricia Martín, Fernando Jiménez, María Jesús Téllez, José Miguel Rosales-Zábal, Silvia García-Bujalance, Juan A. Pineda, María Magdalena Lara-Pérez, Francisco Téllez, Marcial Delgado, Pilar Rincón, Francisco Javier Rodríguez, Roberto Alonso, José De Juan, Antonio García-Herola, María Dolores Espinosa, Antonio Collado, Francisco Jesús Vera-Méndez, Rosario Hernández, José Joaquin Antón, Miguel Ángel Von-Wichmann, Miguel García-Deltoro, Isabel García-Arata, Felicitas Diaz-Flores, Mohamed Omar Balghata, Instituto de Salud Carlos III, European Commission, Fundación Progreso y Salud, Junta de Andalucía, and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
- Subjects
Cyclopropanes ,Male ,0301 basic medicine ,Pyrrolidines ,Sustained Virologic Response ,Sofosbuvir ,Resistance testing ,Hepacivirus ,Viral Nonstructural Proteins ,Direct-acting antivirals ,chemistry.chemical_compound ,0302 clinical medicine ,Resistance-associated substitution ,Anilides ,Prospective Studies ,Sulfonamides ,education.field_of_study ,Imidazoles ,virus diseases ,Valine ,Hepatitis C ,Middle Aged ,Retreatment ,HCV ,Cohort ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,medicine.drug ,Cohort study ,RASs ,medicine.medical_specialty ,Genotype ,Proline ,Lactams, Macrocyclic ,Voxilaprevir ,Population ,Antiviral Agents ,03 medical and health sciences ,Internal medicine ,Drug Resistance, Viral ,Ribavirin ,medicine ,Humans ,education ,Fluorenes ,Ritonavir ,Hepatology ,business.industry ,medicine.disease ,digestive system diseases ,Regimen ,030104 developmental biology ,Treatment failure ,chemistry ,Spain ,Benzimidazoles ,Carbamates ,business - Abstract
GEHEP-004 Study Group: María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Óscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau., [Background & Aims] 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., [Methods] 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., [Results] 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., [Conclusions] 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., [Lay summary] 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., This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040), Fundación Progreso y Salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).
- Published
- 2019