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Journal of Clinical Microbiology, June 2006, p. 1994-1997, Vol. 44, No. 6
0095-1137/06/$08.00+0     doi:10.1128/JCM.02477-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Detection of rtN236T and rtA181V/T Mutations Associated with Resistance to Adefovir Dipivoxil in Samples from Patients with Chronic Hepatitis B Virus Infection by the INNO-LiPA HBV DR Line Probe Assay (Version 2)

Carla Osiowy,1* Jean-Pierre Villeneuve,2 E. Jenny Heathcote,3 Elizabeth Giles,1 and Jamie Borlang1

Public Health Agency of Canada, Winnipeg, Manitoba, Canada,1 Hôpital Saint-Luc du CHUM, Montréal, Quebec, Canada,2 Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada3

Received 30 November 2005/ Returned for modification 17 February 2006/ Accepted 5 April 2006

The nucleotide analog adefovir dipivoxil (ADV) is an effective antiviral treatment for chronic hepatitis B virus (HBV) infection, with resistance to ADV estimated to occur less frequently than resistance to lamivudine treatment. The detection of ADV resistance mutations is necessary during therapy to monitor and anticipate possible treatment failure. The INNO-LiPA HBV DR v2 (LiPA; Innogenetics, Ghent, Belgium) is a DNA hybridization line probe assay for the detection of HBV polymerase mutations associated with resistance to lamivudine and ADV. Evaluation of this assay to detect ADV resistance mutations was performed by analyzing 38 patients treated with ADV. Serial samples taken at 6-month intervals during treatment were available for most patients. A total of 124 samples were analyzed by both LiPA and sequencing. By LiPA analysis, 12 patients (31.5%) were found to have mutations associated with resistance to ADV (rtA181V/T and/or rtN236T). This contrasted with sequence analysis, which found nine patients (24%) with either or both mutations. Twice as many samples were rtN236T positive by LiPA (18 of 124) compared to sequence analysis (9 of 124). LiPA detected the rtN236T mutation at least 6 months earlier than its detection by sequencing in patients for whom consecutive serum samples were available. Although less sensitive, sequencing has the advantage of providing information on other polymerase mutations not represented on LiPA strips. The INNO-LiPA HBV DR v2 assay is a very sensitive and specific assay for the detection of the rtN236T mutation associated with resistance to ADV.

* Corresponding author. Mailing address: Public Health Agency of Canada, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, 1015 Arlington St., Winnipeg, Manitoba R3E 3P6, Canada. Phone: (204) 789-6061. Fax: (204) 789-2082. E-mail: carla_osiowy{at}phac-aspc.gc.ca.

Journal of Clinical Microbiology, June 2006, p. 1994-1997, Vol. 44, No. 6
0095-1137/06/$08.00+0     doi:10.1128/JCM.02477-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jardi, R., Rodriguez-Frias, F., Tabernero, D., Homs, M., Schaper, M., Esteban, R., Buti, M. (2009). Use of the Novel INNO-LiPA Line Probe Assay for Detection of Hepatitis B Virus Variants That Confer Resistance to Entecavir Therapy. J. Clin. Microbiol. 47: 485-488 [Abstract] [Full Text]  
  • Osiowy, C., Gordon, D., Borlang, J., Giles, E., Villeneuve, J.-P. (2008). Hepatitis B virus genotype G epidemiology and co-infection with genotype A in Canada. J. Gen. Virol. 89: 3009-3015 [Abstract] [Full Text]  
  • Libbrecht, E., Doutreloigne, J., Van De Velde, H., Yuen, M.-F., Lai, C.-L., Shapiro, F., Sablon, E. (2007). Evolution of Primary and Compensatory Lamivudine Resistance Mutations in Chronic Hepatitis B Virus-Infected Patients during Long-Term Lamivudine Treatment, Assessed by a Line Probe Assay. J. Clin. Microbiol. 45: 3935-3941 [Abstract] [Full Text]  
  • Valsamakis, A. (2007). Molecular Testing in the Diagnosis and Management of Chronic Hepatitis B. Clin. Microbiol. Rev. 20: 426-439 [Abstract] [Full Text]  


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