TY  - JOUR
A1  - Dietz, Julia
A1  - Rupp, Daniel
A1  - Susser, Simone
A1  - Vermehren, Johannes
A1  - Peiffer, Kai-Henrik
A1  - Filmann, Natalie
A1  - Bon, Dimitra
A1  - Kuntzen, Thomas
A1  - Mauß, Stefan
A1  - Grammatikos, Georgios
A1  - Perner, Dany
A1  - Berkowski, Caterina
A1  - Herrmann, Eva
A1  - Zeuzem, Stefan
A1  - Bartenschlager, Ralf
A1  - Sarrazin, Christoph
T1  - Investigation of NS3 protease resistance-associated variants and phenotypes for the prediction of treatment response to HCV triple therapy
T2  - PLoS One
N2  - Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/41466
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-414668
SN  - 1932-6203
N1  - Copyright: © 2016 Dietz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 11
IS  - (6): e0156731
SP  - 1
EP  - 17
PB  - PLoS
CY  - Lawrence, Kan.
ER  -