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J Clin Virol. 2011 Dec;52(4):321-7. doi: 10.1016/j.jcv.2011.08.015. Epub 2011 Sep 15.

Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir.

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  • 1Klinikum der Goethe Universität, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.



Telaprevir and boceprevir are highly selective hepatitis C virus (HCV) NS3/4A proteaseinhibitors in phase 3 development. Viral breakthrough during mono- and triple-therapies with PEG-interferon and ribavirin and relapse is associated with resistance.


Potential persistence of resistance mutations during long-term follow-up should be analyzed.


Clonal sequence analysis of the NS3-protease gene was performed at long-term follow-up in HCV genotyp-1 infected patients who received telaprevir or boceprevir within phase-1b studies for comparison with resistant variants present directly after the end-of-treatment.


After a median follow-up of 4.2 years in 28 of 82 patients HCV-RNA was still detectable. Resistance variants were detected in two of 14 telaprevir- and in four of 14 boceprevir-treated patients. For telaprevir patients two low-level (V36M, V36A) and one high-level (A156T) mutation associated with resistance were detected at low frequencies (4-9% of the clones). In five boceprevir-treated patients four low level mutations (V36A, T54A/S, V55A) were observed at low frequencies (1-10%) while in one patient additionally a combined variant (T54S+R155K) was detected at 94%. Presence of resistant variants at long-term follow-up was not predictable by variants detected at the end-of-treatment. In one patient a V55A variant which was dominant already at baseline was still detectable at long-term follow-up.


In the majority of patients after short-term treatment with telaprevir or boceprevir wild-type NS3-protease isolates are detectable by clonal sequencing at long-term follow-up. Detectable resistance mutations in single patients are not predictable by initial frequencies of variants.

Copyright © 2011 Elsevier B.V. All rights reserved.

[PubMed - indexed for MEDLINE]
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