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Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

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Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection. / Dietz, Julia; Kalinina, Olga V; Vermehren, Johannes; Peiffer, Kai-Henrik; Matschenz, Katrin; Buggisch, Peter; Niederau, Claus; Schattenberg, Jörn M; Müllhaupt, Beat; Yerly, Sabine; Ringelhan, Marc; Schmid, Roland M; Antoni, Christoph; Müller, Tobias; Schulze Zur Wiesch, Julian; Piecha, Felix; Moradpour, Darius; Deterding, Katja; Wedemeyer, Heiner; Moreno, Christophe; Berg, Thomas; Berg, Christoph P; Zeuzem, Stefan; Welsch, Christoph; Sarrazin, Christoph; European HCV Resistance Study Group.

In: J VIRAL HEPATITIS, Vol. 27, No. 10, 10.2020, p. 974-986.

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

Harvard

Dietz, J, Kalinina, OV, Vermehren, J, Peiffer, K-H, Matschenz, K, Buggisch, P, Niederau, C, Schattenberg, JM, Müllhaupt, B, Yerly, S, Ringelhan, M, Schmid, RM, Antoni, C, Müller, T, Schulze Zur Wiesch, J, Piecha, F, Moradpour, D, Deterding, K, Wedemeyer, H, Moreno, C, Berg, T, Berg, CP, Zeuzem, S, Welsch, C, Sarrazin, C & European HCV Resistance Study Group 2020, 'Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection', J VIRAL HEPATITIS, vol. 27, no. 10, pp. 974-986. https://doi.org/10.1111/jvh.13322

APA

Dietz, J., Kalinina, O. V., Vermehren, J., Peiffer, K-H., Matschenz, K., Buggisch, P., Niederau, C., Schattenberg, J. M., Müllhaupt, B., Yerly, S., Ringelhan, M., Schmid, R. M., Antoni, C., Müller, T., Schulze Zur Wiesch, J., Piecha, F., Moradpour, D., Deterding, K., Wedemeyer, H., ... European HCV Resistance Study Group (2020). Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection. J VIRAL HEPATITIS, 27(10), 974-986. https://doi.org/10.1111/jvh.13322

Vancouver

Dietz J, Kalinina OV, Vermehren J, Peiffer K-H, Matschenz K, Buggisch P et al. Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection. J VIRAL HEPATITIS. 2020 Oct;27(10):974-986. https://doi.org/10.1111/jvh.13322

Bibtex

@article{ab37ca5c69b64b12ae4a8ddf26c9494a,
title = "Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection",
abstract = "Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-na{\"i}ve patients (5%) and the number of NS5A RASs was significantly higher in subtype 4r compared to 4a or 4d (median three RASs vs no or one RAS, respectively, P < .0001). RASsL28V, L30R and M31L pre-existed in subtype 4r and were maintained after NS5Ai failure. Typical subtype 4r RASs were located in subdomain 1a of NS5A, close to membrane interaction and protein-protein interaction sites that are responsible for multimerization and hence viral replication. Retreatment of 37 DAA failure patients was highly effective with 100% SVR in prior SOF/RBV, PI/SOF and PI/NS5Ai failures. Secondary virologic failures were rare (n = 2; subtype 4d and 4r) and only observed in prior NS5Ai/SOF failures (SVR 90%). In conclusion, subtype 4r harboured considerably more RASs compared to other subtypes. A resistance-tailored retreatment using first- and second-generation DAAs was highly effective with SVR rates ≥90% across all subtypes and first-line treatment regimens.",
author = "Julia Dietz and Kalinina, {Olga V} and Johannes Vermehren and Kai-Henrik Peiffer and Katrin Matschenz and Peter Buggisch and Claus Niederau and Schattenberg, {J{\"o}rn M} and Beat M{\"u}llhaupt and Sabine Yerly and Marc Ringelhan and Schmid, {Roland M} and Christoph Antoni and Tobias M{\"u}ller and {Schulze Zur Wiesch}, Julian and Felix Piecha and Darius Moradpour and Katja Deterding and Heiner Wedemeyer and Christophe Moreno and Thomas Berg and Berg, {Christoph P} and Stefan Zeuzem and Christoph Welsch and Christoph Sarrazin and {European HCV Resistance Study Group}",
note = "{\textcopyright} 2020 John Wiley & Sons Ltd.",
year = "2020",
month = oct,
doi = "10.1111/jvh.13322",
language = "English",
volume = "27",
pages = "974--986",
journal = "J VIRAL HEPATITIS",
issn = "1352-0504",
publisher = "Wiley-Blackwell",
number = "10",

}

RIS

TY - JOUR

T1 - Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

AU - Dietz, Julia

AU - Kalinina, Olga V

AU - Vermehren, Johannes

AU - Peiffer, Kai-Henrik

AU - Matschenz, Katrin

AU - Buggisch, Peter

AU - Niederau, Claus

AU - Schattenberg, Jörn M

AU - Müllhaupt, Beat

AU - Yerly, Sabine

AU - Ringelhan, Marc

AU - Schmid, Roland M

AU - Antoni, Christoph

AU - Müller, Tobias

AU - Schulze Zur Wiesch, Julian

AU - Piecha, Felix

AU - Moradpour, Darius

AU - Deterding, Katja

AU - Wedemeyer, Heiner

AU - Moreno, Christophe

AU - Berg, Thomas

AU - Berg, Christoph P

AU - Zeuzem, Stefan

AU - Welsch, Christoph

AU - Sarrazin, Christoph

AU - European HCV Resistance Study Group

N1 - © 2020 John Wiley & Sons Ltd.

PY - 2020/10

Y1 - 2020/10

N2 - Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-naïve patients (5%) and the number of NS5A RASs was significantly higher in subtype 4r compared to 4a or 4d (median three RASs vs no or one RAS, respectively, P < .0001). RASsL28V, L30R and M31L pre-existed in subtype 4r and were maintained after NS5Ai failure. Typical subtype 4r RASs were located in subdomain 1a of NS5A, close to membrane interaction and protein-protein interaction sites that are responsible for multimerization and hence viral replication. Retreatment of 37 DAA failure patients was highly effective with 100% SVR in prior SOF/RBV, PI/SOF and PI/NS5Ai failures. Secondary virologic failures were rare (n = 2; subtype 4d and 4r) and only observed in prior NS5Ai/SOF failures (SVR 90%). In conclusion, subtype 4r harboured considerably more RASs compared to other subtypes. A resistance-tailored retreatment using first- and second-generation DAAs was highly effective with SVR rates ≥90% across all subtypes and first-line treatment regimens.

AB - Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-naïve patients (5%) and the number of NS5A RASs was significantly higher in subtype 4r compared to 4a or 4d (median three RASs vs no or one RAS, respectively, P < .0001). RASsL28V, L30R and M31L pre-existed in subtype 4r and were maintained after NS5Ai failure. Typical subtype 4r RASs were located in subdomain 1a of NS5A, close to membrane interaction and protein-protein interaction sites that are responsible for multimerization and hence viral replication. Retreatment of 37 DAA failure patients was highly effective with 100% SVR in prior SOF/RBV, PI/SOF and PI/NS5Ai failures. Secondary virologic failures were rare (n = 2; subtype 4d and 4r) and only observed in prior NS5Ai/SOF failures (SVR 90%). In conclusion, subtype 4r harboured considerably more RASs compared to other subtypes. A resistance-tailored retreatment using first- and second-generation DAAs was highly effective with SVR rates ≥90% across all subtypes and first-line treatment regimens.

U2 - 10.1111/jvh.13322

DO - 10.1111/jvh.13322

M3 - SCORING: Journal article

C2 - 32396998

VL - 27

SP - 974

EP - 986

JO - J VIRAL HEPATITIS

JF - J VIRAL HEPATITIS

SN - 1352-0504

IS - 10

ER -