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

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Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. / Dietz, Julia; Di Maio, Velia Chiara; de Salazar, Adolfo; Merino, Dolores; Vermehren, Johannes; Paolucci, Stefania; Kremer, Andreas E; Lara, Magdalena; Pardo, Maria Rodriguez; Zoller, Heinz; Degasperi, Elisabetta; Peiffer, Kai-Henrik; Sighinolfi, Laura; Téllez, Francisco; Graf, Christiana; Ghisetti, Valeria; Schreiber, Jonas; Fernández-Fuertes, Elisa; Boglione, Lucio; Muñoz-Medina, Leopoldo; Stauber, Rudolf; Gennari, William; Figueruela, Blanca; Santos, Jesús; Lampertico, Pietro; Zeuzem, Stefan; Ceccherini-Silberstein, Francesca; García, Federico; Sarrazin, Christoph; HCV Virology Italian Resistance Network (VIRONET-C) collaborators.

In: J HEPATOL, Vol. 74, No. 4, 04.2021, p. 801-810.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dietz, J, Di Maio, VC, de Salazar, A, Merino, D, Vermehren, J, Paolucci, S, Kremer, AE, Lara, M, Pardo, MR, Zoller, H, Degasperi, E, Peiffer, K-H, Sighinolfi, L, Téllez, F, Graf, C, Ghisetti, V, Schreiber, J, Fernández-Fuertes, E, Boglione, L, Muñoz-Medina, L, Stauber, R, Gennari, W, Figueruela, B, Santos, J, Lampertico, P, Zeuzem, S, Ceccherini-Silberstein, F, García, F, Sarrazin, C & HCV Virology Italian Resistance Network (VIRONET-C) collaborators 2021, 'Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy', J HEPATOL, vol. 74, no. 4, pp. 801-810. https://doi.org/10.1016/j.jhep.2020.11.017

APA

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., Téllez, F., Graf, C., Ghisetti, V., Schreiber, J., Fernández-Fuertes, E., Boglione, L., ... HCV Virology Italian Resistance Network (VIRONET-C) collaborators (2021). Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. J HEPATOL, 74(4), 801-810. https://doi.org/10.1016/j.jhep.2020.11.017

Vancouver

Dietz J, Di Maio VC, de Salazar A, Merino D, Vermehren J, Paolucci S et al. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. J HEPATOL. 2021 Apr;74(4):801-810. https://doi.org/10.1016/j.jhep.2020.11.017

Bibtex

@article{8221ea71d3d3459299e5b943002b8165,
title = "Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy",
abstract = "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%).",
keywords = "Antiviral Agents/administration & dosage, Carbamates/administration & dosage, Drug Combinations, Drug Resistance, Multiple, Viral/drug effects, Drug Therapy, Combination/methods, Europe/epidemiology, Female, Hepacivirus/drug effects, Hepatitis C, Chronic/diagnosis, Heterocyclic Compounds, 4 or More Rings/administration & dosage, Humans, Liver Cirrhosis/diagnosis, Macrocyclic Compounds/administration & dosage, Male, Middle Aged, Retreatment/methods, Sofosbuvir/administration & dosage, Sulfonamides/administration & dosage, Sustained Virologic Response, Treatment Failure, Treatment Outcome",
author = "Julia Dietz and {Di Maio}, {Velia Chiara} and {de Salazar}, Adolfo and Dolores Merino and Johannes Vermehren and Stefania Paolucci and Kremer, {Andreas E} and Magdalena Lara and Pardo, {Maria Rodriguez} and Heinz Zoller and Elisabetta Degasperi and Kai-Henrik Peiffer and Laura Sighinolfi and Francisco T{\'e}llez and Christiana Graf and Valeria Ghisetti and Jonas Schreiber and Elisa Fern{\'a}ndez-Fuertes and Lucio Boglione and Leopoldo Mu{\~n}oz-Medina and Rudolf Stauber and William Gennari and Blanca Figueruela and Jes{\'u}s Santos and Pietro Lampertico and Stefan Zeuzem and Francesca Ceccherini-Silberstein and Federico Garc{\'i}a and Christoph Sarrazin and {HCV Virology Italian Resistance Network (VIRONET-C) collaborators} and {Schulze zur Wiesch}, Julian and Felix Piecha and Lohse, {Ansgar Wilhelm}",
note = "Copyright {\textcopyright} 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2021",
month = apr,
doi = "10.1016/j.jhep.2020.11.017",
language = "English",
volume = "74",
pages = "801--810",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

AU - Dietz, Julia

AU - Di Maio, Velia Chiara

AU - de Salazar, Adolfo

AU - Merino, Dolores

AU - Vermehren, Johannes

AU - Paolucci, Stefania

AU - Kremer, Andreas E

AU - Lara, Magdalena

AU - Pardo, Maria Rodriguez

AU - Zoller, Heinz

AU - Degasperi, Elisabetta

AU - Peiffer, Kai-Henrik

AU - Sighinolfi, Laura

AU - Téllez, Francisco

AU - Graf, Christiana

AU - Ghisetti, Valeria

AU - Schreiber, Jonas

AU - Fernández-Fuertes, Elisa

AU - Boglione, Lucio

AU - Muñoz-Medina, Leopoldo

AU - Stauber, Rudolf

AU - Gennari, William

AU - Figueruela, Blanca

AU - Santos, Jesús

AU - Lampertico, Pietro

AU - Zeuzem, Stefan

AU - Ceccherini-Silberstein, Francesca

AU - García, Federico

AU - Sarrazin, Christoph

AU - HCV Virology Italian Resistance Network (VIRONET-C) collaborators

AU - Schulze zur Wiesch, Julian

AU - Piecha, Felix

AU - Lohse, Ansgar Wilhelm

N1 - Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2021/4

Y1 - 2021/4

N2 - 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%).

AB - 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%).

KW - Antiviral Agents/administration & dosage

KW - Carbamates/administration & dosage

KW - Drug Combinations

KW - Drug Resistance, Multiple, Viral/drug effects

KW - Drug Therapy, Combination/methods

KW - Europe/epidemiology

KW - Female

KW - Hepacivirus/drug effects

KW - Hepatitis C, Chronic/diagnosis

KW - Heterocyclic Compounds, 4 or More Rings/administration & dosage

KW - Humans

KW - Liver Cirrhosis/diagnosis

KW - Macrocyclic Compounds/administration & dosage

KW - Male

KW - Middle Aged

KW - Retreatment/methods

KW - Sofosbuvir/administration & dosage

KW - Sulfonamides/administration & dosage

KW - Sustained Virologic Response

KW - Treatment Failure

KW - Treatment Outcome

U2 - 10.1016/j.jhep.2020.11.017

DO - 10.1016/j.jhep.2020.11.017

M3 - SCORING: Journal article

C2 - 33220331

VL - 74

SP - 801

EP - 810

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 4

ER -