Document Detail

Dynamic and rapid changes in viral quasispecies by UDPS in chronic hepatitis C patients receiving telaprevir-based therapy.
MedLine Citation:
PMID:  23702639     Owner:  NLM     Status:  Publisher    
BACKGROUND: Telaprevir (TVR) is a protease inhibitor (PI) used in chronic hepatitis C treatment with PEG-interferon plus ribavirin. We analyzed the prevalence and kinetic development of TVR resistance upon treatment. METHODS: Twenty-four cirrhotic patients (genotype 1a, n=8; genotype 1b, n=16) previously non-responders to standard therapy were treated with TVR-based therapy. The distribution of TVR-resistant variants was assessed at every HCV-RNA positive time point by 454 ultra-deep pyrosequencing (UDPS) during a mean follow-up period of 9.4 months. RESULTS: A median of 6,837 reads/specimen was studied. Based on control UDPS, we considered mutations as real when present > 0.4%. TVR-resistant variants were found at baseline in 8/24 patients (33.3%). Four of the 24 patients (16.7%), all genotype 1a, did not achieve HCV-RNA < 100 IU/ml between W2 and W12 and stopped treatment. No statistical significant difference was observed in the prevalence of resistant mutants between responders and non-responders (25% (5/20); 75% (3/4), respectively). The proportion of genotype 1a patients with R155K/T/Q at baseline was higher in non-responders than in responders (50% versus 0%). During treatment failure, significant enrichment in V36A/M and R155K/T/Q was observed but their frequency reverted back to baseline after TVR discontinuation. CONCLUSIONS: TVR-resistant variants are widely present at baseline. The presence of TVR resistant mutants at baseline, even in high abundance (>20%), did not always preclude TVR treatment success. The detection of R155K/T/Q at baseline may predict failure in genotype 1a patients. At failure, which occurred in genotype 1a patients, a significant enrichment in V36A/M and R155K/T/Q was observed.
Pascale Trimoulet; Patricia Pinson; Jennifer Papuchon; Juliette Foucher; Julien Vergniol; Faiza Chermak; Linda Wittkop; Nadège Castaing; Wassil Merrouche; Sandrine Reigadas; Mathieu Molimard; Michael Kann; Hervé Fleury; Victor de Lédinghen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-23
Journal Detail:
Title:  Antiviral therapy     Volume:  -     ISSN:  2040-2058     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Laboratoire de Virologie, CHU de Bordeaux, F-33000 Bordeaux, France.
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