Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark: identification of viral resistance mutations

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

Standard

Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark : identification of viral resistance mutations. / Sølund, Christina; Krarup, Henrik; Ramirez, Santseharay; Thielsen, Peter; Røge, Birgit T; Lunding, Suzanne; Barfod, Toke S; Madsen, Lone G; Tarp, Britta; Christensen, Peer B; Gerstoft, Jan; Laursen, Alex L; Bukh, Jens; Weis, Nina; DANHEP Group.

In: PLOS ONE, Vol. 9, No. 12, e113034, 2014, p. 1-20.

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

Harvard

Sølund, C, Krarup, H, Ramirez, S, Thielsen, P, Røge, BT, Lunding, S, Barfod, TS, Madsen, LG, Tarp, B, Christensen, PB, Gerstoft, J, Laursen, AL, Bukh, J, Weis, N & DANHEP Group 2014, 'Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark: identification of viral resistance mutations', PLOS ONE, vol. 9, no. 12, e113034, pp. 1-20. https://doi.org/10.1371/journal.pone.0113034

APA

Sølund, C., Krarup, H., Ramirez, S., Thielsen, P., Røge, B. T., Lunding, S., Barfod, T. S., Madsen, L. G., Tarp, B., Christensen, P. B., Gerstoft, J., Laursen, A. L., Bukh, J., Weis, N., & DANHEP Group (2014). Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark: identification of viral resistance mutations. PLOS ONE, 9(12), 1-20. [e113034]. https://doi.org/10.1371/journal.pone.0113034

Vancouver

Sølund C, Krarup H, Ramirez S, Thielsen P, Røge BT, Lunding S et al. Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark: identification of viral resistance mutations. PLOS ONE. 2014;9(12):1-20. e113034. https://doi.org/10.1371/journal.pone.0113034

Author

Sølund, Christina ; Krarup, Henrik ; Ramirez, Santseharay ; Thielsen, Peter ; Røge, Birgit T ; Lunding, Suzanne ; Barfod, Toke S ; Madsen, Lone G ; Tarp, Britta ; Christensen, Peer B ; Gerstoft, Jan ; Laursen, Alex L ; Bukh, Jens ; Weis, Nina ; DANHEP Group. / Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark : identification of viral resistance mutations. In: PLOS ONE. 2014 ; Vol. 9, No. 12. pp. 1-20.

Bibtex

@article{801837e39e6a499b9f15af6ef219a82a,
title = "Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark: identification of viral resistance mutations",
abstract = "BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting.METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy.RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively.CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.",
author = "Christina S{\o}lund and Henrik Krarup and Santseharay Ramirez and Peter Thielsen and R{\o}ge, {Birgit T} and Suzanne Lunding and Barfod, {Toke S} and Madsen, {Lone G} and Britta Tarp and Christensen, {Peer B} and Jan Gerstoft and Laursen, {Alex L} and Jens Bukh and Nina Weis and {DANHEP Group}",
year = "2014",
doi = "10.1371/journal.pone.0113034",
language = "English",
volume = "9",
pages = "1--20",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark

T2 - identification of viral resistance mutations

AU - Sølund, Christina

AU - Krarup, Henrik

AU - Ramirez, Santseharay

AU - Thielsen, Peter

AU - Røge, Birgit T

AU - Lunding, Suzanne

AU - Barfod, Toke S

AU - Madsen, Lone G

AU - Tarp, Britta

AU - Christensen, Peer B

AU - Gerstoft, Jan

AU - Laursen, Alex L

AU - Bukh, Jens

AU - Weis, Nina

AU - DANHEP Group

PY - 2014

Y1 - 2014

N2 - BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting.METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy.RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively.CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.

AB - BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting.METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy.RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively.CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.

U2 - 10.1371/journal.pone.0113034

DO - 10.1371/journal.pone.0113034

M3 - Journal article

C2 - 25438153

VL - 9

SP - 1

EP - 20

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 12

M1 - e113034

ER -

ID: 131070829