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

Dietz, Julia; Maio, V.C. Di; Salazar, Adolfo de; 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, Féderico; Sarrazin, Christoph; Aghemo, Alessio; Allice, Tiziano; Andreoni, Massimo; Angélico, M.; Baldanti, Fausto; Barbaliscia, Silvia; Bertoli, Ada; Borghi, Vanni; Calvaruso, V.; Castaldo, Giuseppe; Craxı̀, Antonio; Francioso, S.; Perno, Carlo Federico; Pozzoni, Pietro; Toniutto, Pier Luigi; Zazzi, Maurizio; Pérez, Ana Belén Macho; Quílez, Cristina; Alados, Juan Carlos; Cabezas, Joaquín; Ruiz-Tapiador, Juan Ignacio Arenas; Jiménez, Miguel; Pascasio-Acevedo, Juan Manuel; Rodrı́guez, Manuel; Zábal, José Miguel Rosales; Deltoro, Miguel García; Sapiña, Ana María Martinez; Fuentes, Ana; Chueca, Natalia; Berg, Christoph P.; Herrmann, Andreas; Stallmach, Andreas; Port, Kerstin; Deterding, M. Katja; Wedermeyer, Heiner; Cornberg, Markus; Manns, Michael P.; Moreno, Christophe; Wiesch, Julian Schulze zur; Piecha, Felix; Lohse, Ansgar W.; Siebler, Jürgen; Kordecki, Nikolaus; Magenta, Lorenzo; Jäger, Bürkard; Möller, Hjördis; Heyne, R.; Beyer, Tomas; Grunwald, Stephan; Baumgarten, Axels; Jägel-Guedes, Eva; Schmidt, Wolfgang

doi:10.1016/j.jhep.2020.11.017

Cited by 31 publications

(35 citation statements)

References 42 publications

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“…Retrospective data on retreatment efficacy was included in a subgroup of patients. 37 As in previous studies, resistance analysis within NS3, NS5A and NS5B genes before and after VOX/VEL/SOF failure showed only minor changes in RAS frequencies and profiles. 37,59 In line with data on characteristics of VOX/VEL/SOF failures, most patients were infected with HCV genotype 3 (45%) and had cirrhosis (70%).…”

Section: Retreatment After Vox/vel/sof Failure As Rescue Treatmentsupporting

confidence: 78%

“…37 As in previous studies, resistance analysis within NS3, NS5A and NS5B genes before and after VOX/VEL/SOF failure showed only minor changes in RAS frequencies and profiles. 37,59 In line with data on characteristics of VOX/VEL/SOF failures, most patients were infected with HCV genotype 3 (45%) and had cirrhosis (70%). Rescue treatments included G/P+SOF with or without ribavirin (n = 15), G/P alone (n = 2), VOX/VEL/SOF with or without ribavirin (n = 4) and VEL/SOF plus ribavirin (n = 1), all for 12 to 24 weeks.…”

Section: Retreatment After Vox/vel/sof Failure As Rescue Treatmentsupporting

confidence: 78%

“…2). 16,19,25,29,[33][34][35][36][37][38] Overall, RAS patterns are partially overlapping for the different NS3 and NS5A inhibitors. However, there are also differences with non-overlapping resistance profiles which may be important for selection of rescue DAA regimens.…”

Section: Key Pointmentioning

confidence: 96%

“…Other RASs also have been detected in individual patients. For HCV genotypes 2-6 RASs selected depend substantially on HCV subtypes 16,19,25,29,[33][34][35][36][37][38]. DAA, direct-acting antiviral; DAC, daclatasvir; DSV, dasabuvir; EBV, elbasvir; GLE, glecaprevir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; Non-NUC, non-nucleosidic NS5B polymerase inhibitor; NUC, nucleotide NS5B polymerase inhibitor; OMV, ombitasvir; PIB, pibrentasvir; PTVr, paritaprevir/ritonavir; RASs, resistance-associated substitutions; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.…”

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confidence: 99%

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Treatment failure with DAA therapy: Importance of resistance

Sarrazin¹

2021

Journal of Hepatology

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Viral resistance is a major reason for virological failure in patients being treated with direct-acting antivirals (DAAs) for chronic HCV infection. However, the importance of viral resistance mainly depends on the DAA regimen and HCV genotype. For first-line therapy with glecaprevir/pibrentasvir (G/P) or velpatasvir/sofosbuvir (VEL/SOF) no general baseline resistance analysis is required because of the high antiviral activity and high barrier to resistance. If available, resistance testing may help to optimise therapy in certain subgroups of patients with HCV genotype 3 and other rare HCV geno/subtypes. Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is the first choice for the second-line treatment of patients following a previous DAA failure, with rates of viral eradication above 90% irrespective of the presence of resistance-associated substitutions (RASs). However, in resource-limited settings, only firstgeneration DAAs may be available for second-line therapy. Here, RASs selected during initial antiviral therapy should be considered if testing is available and rescue treatment should include a switch to a regimen with a new DAA class to optimise treatment response. Patients with HCV genotype 3 are overrepresented in the group who experience DAA treatment failure. Limited data are available for thirdline therapies, but promising results have been achieved with G/P plus SOF or VOX/VEL/SOF with or without ribavirin for 12 to 24 weeks; these regimens should be administered irrespective of a patient's RAS profile.

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Section: Retreatment After Vox/vel/sof Failure As Rescue Treatmentsupporting

confidence: 78%

Section: Retreatment After Vox/vel/sof Failure As Rescue Treatmentsupporting

confidence: 78%

Section: Key Pointmentioning

confidence: 96%

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confidence: 99%

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Treatment failure with DAA therapy: Importance of resistance

Sarrazin¹

2021

Journal of Hepatology

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“…In line with the experience of Martin et al, we also reported high SVR rates for patients who received G/P+SOF±RBV as thirdline rescue treatment. 3 We are pleased to now be able to report an update on the final treatment outcome of the patients treated in our study, since we have received the follow-up data from the last pending patient. In the published work, the final treatment outcome was available for 21 of 22 patients who had received rescue treatment.…”

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confidence: 99%