Open Access Short report

Compensatory substitutions in the HCV NS3/4A protease cleavage sites are not observed in patients treated unsuccessfully with telaprevir combination treatment

James C Sullivan, Eileen Z Zhang, Doug J Bartels, Ann Tigges, Jennifer L Dorrian, Ann D Kwong and Tara L Kieffer*

Author Affiliations

Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA

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Virology Journal 2012, 9:147  doi:10.1186/1743-422X-9-147

Published: 6 August 2012



Development of compensatory mutations within the HIV p7/p1 and p1/p6 protease cleavage site region has been observed in HIV-infected patients treated with protease inhibitors. Mechanisms of fitness compensation may occur in HCV populations upon treatment of HCV protease inhibitors as well.


In this study, we investigated whether substitutions in protease cleavage site regions of HCV occur in response to a treatment regimen containing the NS3/4A protease inhibitor telaprevir (TVR). Evaluation of viral populations from 569 patients prior to treatment showed that the four NS3/4A cleavage sites were well conserved. Few changes in the cleavage site regions were observed in the 159 patients who failed TVR combination treatment, and no residues displayed evidence of directional selection after the acquisition of TVR-resistance.


Cleavage site mutations did not occur after treatment with the HCV protease inhibitor telaprevir.

Directional selection; Fitness; INCIVEK; Telaprevir