Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

Autor: Ada Bertoli, Michael P. Manns, M. Katja Deterding, Vanni Borghi, Silvia Barbaliscia, Elisabetta Degasperi, Julian Schulze zur Wiesch, Velia Chiara Di Maio, Ansgar W. Lohse, Wolfgang Schmidt, Markus Cornberg, Christophe Moreno, Tomas Beyer, Federico García, Johannes Vermehren, Pietro Lampertico, Andreas E. Kremer, Laura Sighinolfi, Felix Piecha, Magdalena Lara, Pier Luigi Toniutto, Christoph Sarrazin, Antonio Craxì, Francesca Ceccherini-Silberstein, Jonas Schreiber, Jesús Santos, Ana Belén Pérez, Alessio Aghemo, William Gennari, Lorenzo Magenta, Manuel Alberto Macias Rodriguez, Heiner Wedermeyer, Ana Fuentes, Stephan Grunwald, Jose Miguel Rosales Zabal, Francisco Téllez, Dolores Merino, Burkhard Jäger, Miguel García Deltoro, Juan Manuel Pascasio-Acevedo, Blanca Figueruela, Andreas Stallmach, Renate Heyne, Valeria Ghisetti, Christoph P. Berg, Carlo Federico Perno, Elisa Fernández-Fuertes, Nikolaus Kordecki, Ana María Martinez Sapiña, Natalia Chueca, Andreas Herrmann, Eva Jägel-Guedes, Vincenza Calvaruso, Maurizio Zazzi, Massimo Andreoni, Lucio Boglione, Mario Angelico, Simona Francioso, Giuseppe Cariti, Cristina Quilez, Tiziano Allice, Christiana Graf, Leopoldo Muñoz-Medina, Fausto Baldanti, Rudolf E. Stauber, Jürgen Siebler, Julia Dietz, Maria Josefa Rodriguez Pardo, Kerstin Port, Heinz Zoller, Juan Carlos Alados, Stefan Zeuzem, Juan Ignacio Arenas Ruiz-Tapiador, Joaquín Cabezas, Stefania Paolucci, Axels Baumgarten, Kai-Henrik Peiffer, Adolfo de Salazar, Pietro Pozzoni, Miguel Jimenez, Hjördis Möller
Přispěvatelé: Dietz J., Di Maio V.C., de Salazar A., Merino D., Vermehren J., Paolucci S., Kremer A.E., Lara M., Pardo M.R., Zoller H., Degasperi E., Peiffer K.-H., Sighinolfi L., Tellez F., Graf C., Ghisetti V., Schreiber J., Fernandez-Fuertes E., Boglione L., Munoz-Medina L., Stauber R., Gennari W., Figueruela B., Santos J., Lampertico P., Zeuzem S., Ceccherini-Silberstein F., Garcia F., Sarrazin C., Aghemo A., Allice T., Andreoni M., Angelico M., Baldanti F., Barbaliscia S., Bertoli A., Borghi V., Calvaruso V., Cariti G., Craxi A., Francioso S., Perno C.F., Pozzoni P., Toniutto P.L., Zazzi M., Perez A.B., Quilez C., Alados J.C., Cabezas J., Ruiz-Tapiador J.I.A., Jimenez M., Pascasio-Acevedo J.M., Rodriguez M.A.M., Zabal J.M.R., Deltoro M.G., Sapina A.M.M., Fuentes A., Chueca N., Berg C.P., Herrmann A., Stallmach A., Port K., Katja Deterding M., Wedermeyer H., Cornberg M., Manns M.P., Moreno C., Wiesch J.S.Z., Piecha F., Lohse A., Siebler J., Kordecki N., Magenta L., Jager B., Moller H., Heyne R., Beyer T., Grunwald S., Baumgarten A., Jagel-Guedes E., Schmidt W.
Rok vydání: 2021
Předmět:
Zdroj: Journal of Hepatology. 74:801-810
ISSN: 0168-8278
Popis: Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. Conclusions VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. Lay summary The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).
Databáze: OpenAIRE
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