Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1–3 Infections

Dietz, Julia; Spengler, Ulrich; Müllhaupt, Beat; Wiesch, Julian Schulze zur; Piecha, Felix; Mauss, Stefan; Seegers, Barbara; Hinrichsen, Holger; Antoni, Christoph; Wietzke‐Braun, Perdita; Peiffer, Kai‐Henrik; Berger, Annemarie; Matschenz, K; Buggisch, Peter; Backhus, J; Zizer, Eugen; Böettler, Tobias; Semela, David; Stauber, Rudolf; Berg, Thomas; Berg, Christoph P.; Zeuzem, Stefan; Vermehren, Johannes; Sarrazin, Christoph

doi:10.1016/j.cgh.2019.10.051

Cited by 13 publications

(16 citation statements)

References 8 publications

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“…Still, the most frequently used DAA re-treatment option at our center was sofosbuvir/velpatasvir/voxilaprevir, which yielded excellent results despite the difficult to treat population, including the presence of baseline RAS. In this context, larger studies need to clarify the role of RAS testing before the initiation of DAA re-treatment [23,24], as RAS did not seem to affect re-treatment results in our small sample. This is especially interesting as RAS testing was mostly carried out in patients in whom RAS were a priori hypothesized to be relevant.…”

Section: Sof/ldv+rbv [Svr%]mentioning

confidence: 84%

“…PCR products were population-based sequenced on an ABI Prism 3130xl Genetic Analyzer (Applied Biosystems, Foster City, CA). Details on primers, PCR conditions, sequencing as well as on the analysis of relevant RASs have been published previously [14,15]. The sensitivity of population-based sequencing is approximately 15% for minority HCV variants in the quasispecies [16].…”

Section: Amplification and Sequencing Analysismentioning

confidence: 99%

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Treatment and re-treatment results of HCV patients in the DAA era

et al. 2020

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Background Re-treatment in patients with a chronic hepatitis C virus (HCV) infection and a previous failure to direct-acting antiviral (DAA) treatment remains a challenge. Therefore, we investigated the success rate of treatment and re-treatment regimens used at our center from October 2011 to March 2018. Methods A retrospective analysis of DAA-based HCV therapies of 1096 patients was conducted. Factors associated with a virological relapse were identified by univariable and multivariable logistic regression, treatment success of the re-treatment regimens was evaluated by an analysis of sustained virological response (SVR) rates in patients with a documented followup 12 weeks after the end of treatment. Results Of 1096 patients treated with DAA-based regimens, 91 patients (8%) were lost to follow-up, 892 of the remaining 1005 patients (89%) achieved an SVR12. Most patients (65/113, 58%) who experienced a virological relapse received an interferon-based DAA regimen. SVR rates were comparable in special cohorts like liver transplant recipients (53/61, 87%) and people with a human immunodeficiency virus (HIV) coinfection (41/45, 91%). On multivariable analysis, interferon-based DAA therapy was associated with treatment failure (odds ratio 0.111, 95%-confidence interval 0.054-0.218) among others. One hundred seventeen patients with multiple DAA treatment courses were identified, of which 97 patients (83%) experienced a single relapse, but further relapses after two (18/117, 15%) or even three (2/ 117, 2%) treatment courses were also observed. Eighty-two of 96 (85%) re-treatment attempts with all-oral DAA regimens were successful after an initial treatment failure.

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Section: Sof/ldv+rbv [Svr%]mentioning

confidence: 84%

Section: Amplification and Sequencing Analysismentioning

confidence: 99%

Treatment and re-treatment results of HCV patients in the DAA era

et al. 2020

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“…Generally, this regimen shows a high barrier to resistance but as for the other pangenotypic regimens, HCV genotype 3 seems to be overrepresented in patients experiencing virologic failure. 17,18 Given the broad use of daclatasvir in many countries, studies on the importance of resistance would be desirable.…”

Section: Introductionmentioning

confidence: 99%

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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“…Eine Wiederholung des eingesetzten DAA-Therapieregimes ohne Beachtung von viralen Resistenzen ist nicht zu empfehlen [98,99]…”

Section: Erläuterungenunclassified