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Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

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Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure. / Dietz, Julia; Müllhaupt, Beat; Buggisch, Peter; Graf, Christiana; Peiffer, Kai-Henrik; Matschenz, Katrin; Schattenberg, Jörn M; Antoni, Christoph; Mauss, Stefan; Niederau, Claus; Discher, Thomas; Trauth, Janina; Dultz, Georg; Schulze Zur Wiesch, Julian; Piecha, Felix; Klinker, Hartwig; Müller, Tobias; Berg, Thomas; Neumann-Haefelin, Christoph; Berg, Christoph P; Zeuzem, Stefan; Sarrazin, Christoph; German HCV Resistance Study Group.

In: J HEPATOL, Vol. 78, No. 1, 01.2023, p. 57-66.

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

Harvard

Dietz, J, Müllhaupt, B, Buggisch, P, Graf, C, Peiffer, K-H, Matschenz, K, Schattenberg, JM, Antoni, C, Mauss, S, Niederau, C, Discher, T, Trauth, J, Dultz, G, Schulze Zur Wiesch, J, Piecha, F, Klinker, H, Müller, T, Berg, T, Neumann-Haefelin, C, Berg, CP, Zeuzem, S, Sarrazin, C & German HCV Resistance Study Group 2023, 'Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure', J HEPATOL, vol. 78, no. 1, pp. 57-66. https://doi.org/10.1016/j.jhep.2022.08.016

APA

Dietz, J., Müllhaupt, B., Buggisch, P., Graf, C., Peiffer, K-H., Matschenz, K., Schattenberg, J. M., Antoni, C., Mauss, S., Niederau, C., Discher, T., Trauth, J., Dultz, G., Schulze Zur Wiesch, J., Piecha, F., Klinker, H., Müller, T., Berg, T., Neumann-Haefelin, C., ... German HCV Resistance Study Group (2023). Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure. J HEPATOL, 78(1), 57-66. https://doi.org/10.1016/j.jhep.2022.08.016

Vancouver

Dietz J, Müllhaupt B, Buggisch P, Graf C, Peiffer K-H, Matschenz K et al. Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure. J HEPATOL. 2023 Jan;78(1):57-66. https://doi.org/10.1016/j.jhep.2022.08.016

Bibtex

@article{3a0f6f917e0f45f1a1b416615b8e03a4,
title = "Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure",
abstract = "BACKGROUND & AIMS: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).METHODS: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.RESULTS: A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.CONCLUSIONS: We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.IMPACT AND IMPLICATIONS: There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.",
keywords = "Humans, Antiviral Agents/pharmacology, Drug Resistance, Viral/genetics, Viral Nonstructural Proteins/genetics, Genotype, Hepatitis C, Chronic/drug therapy, Hepacivirus/genetics, Treatment Failure",
author = "Julia Dietz and Beat M{\"u}llhaupt and Peter Buggisch and Christiana Graf and Kai-Henrik Peiffer and Katrin Matschenz and Schattenberg, {J{\"o}rn M} and Christoph Antoni and Stefan Mauss and Claus Niederau and Thomas Discher and Janina Trauth and Georg Dultz and {Schulze Zur Wiesch}, Julian and Felix Piecha and Hartwig Klinker and Tobias M{\"u}ller and Thomas Berg and Christoph Neumann-Haefelin and Berg, {Christoph P} and Stefan Zeuzem and Christoph Sarrazin and {German HCV Resistance Study Group} and Sabine Jordan and {von Felden}, Johann and Lohse, {Ansgar Wilhelm}",
note = "Copyright {\textcopyright} 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2023",
month = jan,
doi = "10.1016/j.jhep.2022.08.016",
language = "English",
volume = "78",
pages = "57--66",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

AU - Dietz, Julia

AU - Müllhaupt, Beat

AU - Buggisch, Peter

AU - Graf, Christiana

AU - Peiffer, Kai-Henrik

AU - Matschenz, Katrin

AU - Schattenberg, Jörn M

AU - Antoni, Christoph

AU - Mauss, Stefan

AU - Niederau, Claus

AU - Discher, Thomas

AU - Trauth, Janina

AU - Dultz, Georg

AU - Schulze Zur Wiesch, Julian

AU - Piecha, Felix

AU - Klinker, Hartwig

AU - Müller, Tobias

AU - Berg, Thomas

AU - Neumann-Haefelin, Christoph

AU - Berg, Christoph P

AU - Zeuzem, Stefan

AU - Sarrazin, Christoph

AU - German HCV Resistance Study Group

AU - Jordan, Sabine

AU - von Felden, Johann

AU - Lohse, Ansgar Wilhelm

N1 - Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2023/1

Y1 - 2023/1

N2 - BACKGROUND & AIMS: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).METHODS: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.RESULTS: A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.CONCLUSIONS: We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.IMPACT AND IMPLICATIONS: There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

AB - BACKGROUND & AIMS: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).METHODS: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.RESULTS: A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.CONCLUSIONS: We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.IMPACT AND IMPLICATIONS: There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

KW - Humans

KW - Antiviral Agents/pharmacology

KW - Drug Resistance, Viral/genetics

KW - Viral Nonstructural Proteins/genetics

KW - Genotype

KW - Hepatitis C, Chronic/drug therapy

KW - Hepacivirus/genetics

KW - Treatment Failure

U2 - 10.1016/j.jhep.2022.08.016

DO - 10.1016/j.jhep.2022.08.016

M3 - SCORING: Journal article

C2 - 36031158

VL - 78

SP - 57

EP - 66

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 1

ER -