BACKGROUND: Population sequencing (PS) has shown that telaprevir-resistant variants are not typically detectable at baseline (prevalence, ≤5% of patients), and most variants present at the time of treatment failure are no longer detectable at the end of the study. METHODS: To gain insight into the evolution of telaprevir-resistant variants, their baseline prevalence and persistence after treatment was investigated using a more sensitive, deep-sequencing (DS) technique in a large number of treatment-experienced patients from the REALIZE study who were infected with hepatitis C virus genotype 1. RESULTS: Before treatment initiation, telaprevir-resistant variants (T54A, T54S, or R155K in 1%-2% of the viral population) were detected by DS in a fraction (2%) of patients for whom PS failed to detect resistance; these variants were not necessarily detected at the time of treatment failure. Of 49 patients in whom telaprevir-resistant variants were detected by PS at the time of treatment failure but not at the end of the study, DS revealed the presence of variants (V36A/L/M, T54S, or R155K in 1%-36% of the viral population) in 16 patients (33%) at the end of the study. CONCLUSIONS: Similar to PS findings, DS analysis revealed that the frequency of telaprevir-resistant variants before treatment was also low, and variants detected at the time of treatment failure were no longer detectable in the majority of patients during follow-up.
RCT Entities:
BACKGROUND: Population sequencing (PS) has shown that telaprevir-resistant variants are not typically detectable at baseline (prevalence, ≤5% of patients), and most variants present at the time of treatment failure are no longer detectable at the end of the study. METHODS: To gain insight into the evolution of telaprevir-resistant variants, their baseline prevalence and persistence after treatment was investigated using a more sensitive, deep-sequencing (DS) technique in a large number of treatment-experienced patients from the REALIZE study who were infected with hepatitis C virus genotype 1. RESULTS: Before treatment initiation, telaprevir-resistant variants (T54A, T54S, or R155K in 1%-2% of the viral population) were detected by DS in a fraction (2%) of patients for whom PS failed to detect resistance; these variants were not necessarily detected at the time of treatment failure. Of 49 patients in whom telaprevir-resistant variants were detected by PS at the time of treatment failure but not at the end of the study, DS revealed the presence of variants (V36A/L/M, T54S, or R155K in 1%-36% of the viral population) in 16 patients (33%) at the end of the study. CONCLUSIONS: Similar to PS findings, DS analysis revealed that the frequency of telaprevir-resistant variants before treatment was also low, and variants detected at the time of treatment failure were no longer detectable in the majority of patients during follow-up.
Authors: Bart Fevery; Kim Thys; Veerle Van Eygen; Thierry Verbinnen; Elizabeth Van Rossem; Annemie Buelens; Jeroen Aerssens; James Witek; Gaston Picchio; Sandra De Meyer; Oliver Lenz Journal: Open Forum Infect Dis Date: 2016-03-14 Impact factor: 3.835
Authors: Julia Dietz; Daniel Rupp; Simone Susser; Johannes Vermehren; Kai-Henrik Peiffer; Natalie Filmann; Dimitra Bon; Thomas Kuntzen; Stefan Mauss; Georgios Grammatikos; Dany Perner; Caterina Berkowski; Eva Herrmann; Stefan Zeuzem; Ralf Bartenschlager; Christoph Sarrazin Journal: PLoS One Date: 2016-06-09 Impact factor: 3.240
Authors: Leen Vijgen; Kim Thys; An Vandebosch; Pieter Van Remoortere; René Verloes; Sandra De Meyer Journal: Virol J Date: 2017-05-31 Impact factor: 4.099