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