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Abstract Details
Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy
J Hepatol. 2020 Nov 18;S0168-8278(20)33770-3. doi: 10.1016/j.jhep.2020.11.017.Online ahead of print.
Julia Dietz1, Velia Chiara Di Maio2, Adolfo de Salazar3, Dolores Merino4, Johannes Vermehren1, Stefania Paolucci5, Andreas E Kremer6, Magdalena Lara7, Maria Rodriguez Pardo8, Heinz Zoller9, Elisabetta Degasperi10, Kai-Henrik Peiffer1, Laura Sighinolfi11, Francisco Téllez12, Christiana Graf1, Valeria Ghisetti13, Jonas Schreiber14, Elisa Fernández-Fuertes15, Lucio Boglione16, Leopoldo Muñoz-Medina17, Rudolf Stauber18, William Gennari19, Blanca Figueruela20, Jesús Santos21, Pietro Lampertico10, Stefan Zeuzem1, Francesca Ceccherini-Silberstein2, Federico García3, Christoph Sarrazin22
Author information
1Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany.
2Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
3Department of Clinical Microbiology, Hospital Universitario San Cecilio, Instituto de Investigación Ibs, Granada, Spain.
4Infectious Diseases Unit, Hospital Juan Ramón Jiménez, Spain.
5Molecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinic Foundation San Matteo, Pavia, Italy.
6Department of Medicine I, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
7Hospital Nuestra Sra de Candelaria, Tenerife, Spain.
8Hospital Universitario Puerta del Mar, Cádiz, Spain.
9Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.
10Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
11University Hospital of Ferrara, Ferrara, Italy.
12Infectious Diseases Unit, University Hospital of Puerto Real, Cádiz, Spain.
13Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, ASL Città di Torino, Turin, Italy.
14Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
15Infectious Diseases Unit, Hospital de Poniente, El Ejido, Almería, Spain.
16Department of Translational Medicine (DiMET), University of Piemonte Orientale, Novara, Italy.
17Department of Infectious Disease, Hospital Universitario San Cecilio, Granada, Spain.
18Department of Internal Medicine, Medical University of Graz, Graz, Austria.
19Microbiology Unit, University Hospital of Modena, Modena, Italy.
20Hospital Universitario Virgen de Valme, Sevilla, Spain.
21Infectious Diseases Unit, Hospital Universitario Virgen de la Victoria, Instituto de Investigación, IBIMA, Málaga, Spain.
22Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany; Medizinische Klinik 2, St. Josefs-Hospital, Wiesbaden, Germany. Electronic address: sarrazin@em.uni-frankfurt.de.
Abstract
Background & aims: Data on patients with chronic hepatitis C virus (HCV) infection who failed voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment and rescue treatment options for these patients are limited.
Methods: Samples of 40 patients with HCV genotypes (GT) 1-4 who failed VOX/VEL/SOF as retreatment 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: The majority of 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 a NS3-inhibitor (30%), a NS5A-inhibitor (100%) and SOF (85%). Baseline RASs available in a subgroup of patients before VOX/VEL/SOF (78%) included rarely NS3 RAS with exception of Q80K in GT1a (40%), typical NS5A RASs pattern in the majority of patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure available in 98% of patients showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n=2) or with sofosbuvir±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 15/19 (79%) patients with final treatment outcome. Of these, two GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF and G/P+SOF+R, respectively, and two 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 RASs pattern within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in the majority of patients.