Doug J. Bartels

TL;DR: Resistant HCV isolates are selected rapidly during therapy with the highly active protease inhibitor telaprevir, and changes in the frequency of mutations after the end of dosing showed an inverse relationship between in vivo viral fitness and resistance.

TL;DR: High levels of naturally occurring protease inhibitor-resistant variants were uncommon in HCV treatment-naive patients, and as new HCV agents are evaluated in clinical trials, it will be important to monitor the effect of baseline variants on sensitivity.

TL;DR: After failure to achieve SVR with TVR-based treatment, resistant variants are observed in most patients, however, presumably due to the lower fitness of those variants, they tend to be replaced with wild-type virus over time.

TL;DR: In general, HCV variants with lower-level resistance to telaprevir were observed as the dominant species in 0 to 3% of patients, depending on the specific variant, whereas higher-level resistant variants (>25-fold-increased IC50) were not observed.

TL;DR: In this article, the authors used purified protease domain proteins and reconstituted HCV subgenomic replicons for phenotypic characterization of substitutions in the NS3 protease domains.