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Canadian Journal of Gastroenterology
Volume 27, Issue 7, Pages 414-416
Original Article

Pretreatment Resistance to Hepatitis C Virus Protease Inhibitors Boceprevir/Telaprevir in Hepatitis C Subgenotype 1A-Infected Patients from Manitoba

Anton Andonov,1 Kamran Kadkhoda,2 Carla Osiowy,1 and Kelly Kaita3

1Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Manitoba, Canada
2Cadham Provincial Laboratory, Winnipeg, Manitoba, Canada
3University of Manitoba, Department of Internal Medicine, Winnipeg, Manitoba, Canada

Received 7 January 2013; Accepted 21 February 2013

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND: Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available.

OBJECTIVE: To detect pre-existing mutations conferring resistance to boceprevir and/or telaprevir in Canadian patients infected with HCV genotype 1a.

METHODS: Resistance-associated mutations (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not yet received antiviral therapy. The NS3 protease gene was sequenced and common RAMs were identified based on a recently published list.

RESULTS: The overall prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared with other similar studies. All of the observed RAMs were associated with a low level of resistance. A surprisingly high proportion of patients had the V55A RAM (10.6%). None of the mutations associated with a high level of resistance were observed. The simultaneous presence of two low-level resistance mutations (V36L and V55A) was observed in only one patient. Three other patients had both T54S RAM and V55I mutations, which may require a higher concentration of the protease drugs. The prevalence of various mutations in Aboriginal Canadian patients was higher (37.5%) compared with Caucasians (16.39%) (P=0.038).

CONCLUSIONS: The present study was the first to investigate pre-existing drug resistance to boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level RAMs, especially patients of Aboriginal descent, which may contribute to an increased risk of treatment failure.