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

Dietz J, Di Maio VC, de Salazar A, Merino D, Vermehren J, Paolucci S, Kremer A, Lara M, Pardo MR, Zoller H, Degasperi E, Peiffer KH, 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, Aghemo A, Allice T, Andreoni M, Angelico M, Baldanti F, Barbaliscia S, Bertoli A, Borghi V, Calvaruso V, Cariti G, Craxì A, Francioso S, Perno CF, Pozzoni P, Toniutto PL, Zazzi M, Pérez AB, Quilez C, Alados JC, Cabezas J, Ruiz-Tapiador JIA, Jimenez M, Pascasio-Acevedo JM, Rodriguez MAM, Zabal JMR, Deltoro MG, Sapiña AMM, Fuentes A, Chueca N, Berg CP, Herrmann A, Stallmach A, Port K, Katja Deterding M, Wedermeyer H, Cornberg M, Manns MP, Moreno C, Wiesch JSz, Piecha F, Lohse A, Kordecki N, Magenta L, Jäger B, Möller H, Heyne R, Beyer T, Grunwald S, Baumgarten A, Jägel-Guedes E, Schmidt W, Siebler J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1016/j.jhep.2020.11.017

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 15/19 (79%) 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 (79%).

Authors with CRIS profile

Involved external institutions

Ospedale Amedeo di Savoia Italy (IT) Hospital Universitario Nuestra Señora de Candelaria (HUNSC) Spain (ES) Hospital Universitario Puerto Real Spain (ES) Hospital Universitario Puerta del Mar Spain (ES) Hospital Juan Ramón Jiménez Spain (ES) Medizinische Universität Innsbruck Austria (AT) Università degli Studi di Ferrara Italy (IT) Università degli Studi di Roma 'Tor Vergata' Italy (IT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of Eastern Piedmont / Università degli Studi del Piemonte Orientale "Amedeo Avogadro" Italy (IT) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Hospital Universitario Virgen de la Victoria Spain (ES) Azienda Socio Sanitaria Territoriale (ASST) Lecco Italy (IT) Hospital Universitario San Cecilio Spain (ES) Università degli Studi di Siena (UNISI) / University of Siena Italy (IT) Policlinico di Modena Italy (IT) Hospitales Universitarios Virgen Macarena y Virgen del Rocío Spain (ES) Humanitas Research Hospital / IRCCS Istituto Clinico Humanitas Italy (IT) Hospital Costa del Sol Spain (ES) Policlinico Tor Vergata Italy (IT) Hospital Universitario Virgen de Valme Spain (ES) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Università degli studi di Milano Italy (IT) Medizinische Universität Graz Austria (AT) Universitätsklinikum Tübingen Germany (DE) Hôpital Erasme Belgium (BE) Hospital de Poniente Spain (ES) Hospital Universitario Miguel Servet Spain (ES) Hospital Marina Baixa Spain (ES) Hospital Universitario Reina Sofía de Córdoba Edificio IMIBIC Spain (ES) Universitätsklinikum Jena Germany (DE) Donostia University Hospital / Donostia Unibertsitate Ospitalea Spain (ES) Hospital General Universitari de València Spain (ES) University of Turin / Università degli Studi di Torino (UNITO) Italy (IT) Università degli Studi di Palermo Italy (IT) University of Udine / Università degli Studi di Udine Italy (IT) Hospital Regional de Málaga Spain (ES) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Italy (IT) ASL Città di Torino Italy (IT) Policlinico San Matteo Pavia Fondazione IRCCS Italy (IT) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) Spain (ES)

How to cite

APA:

Dietz, J., Di Maio, V.C., de Salazar, A., Merino, D., Vermehren, J., Paolucci, S.,... Siebler, J. (2021). Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2020.11.017

MLA:

Dietz, Julia, et al. "Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy." Journal of Hepatology (2021).

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