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

Virology Journal

Tara L Kieffer¹  Ann D Kwong¹  Jennifer L Dorrian¹  Ann Tigges¹  Doug J Bartels¹  Eileen Z Zhang¹  James C Sullivan¹ 

[1] Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA

关键词: Telaprevir;    INCIVEK;    Fitness;    Directional selection;   

Others  :  1154250
DOI  :  10.1186/1743-422X-9-147

 received in 2012-02-01, accepted in 2012-07-18,  发布年份 2012

【 摘 要 】

Background

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.

Findings

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.

Conclusions

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

【 授权许可】

   
2012 Sullivan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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