Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B
Article first published online: 16 JAN 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Medical Virology
Volume 81, Issue 3, pages 417–424, March 2009
How to Cite
Cha, C. K., Kwon, H. C., Cheong, J. Y., Cho, S. W., Hong, S. P., Kim, S.-O. and Yoo, W. D. (2009), Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B. J. Med. Virol., 81: 417–424. doi: 10.1002/jmv.21402
- Issue published online: 16 JAN 2009
- Article first published online: 16 JAN 2009
- Manuscript Accepted: 23 OCT 2008
- Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea. Grant Number: A050021
- hepatitis B virus;
- reverse transcriptase;
- antiviral resistance
Adefovir has a potent antiviral activity as a rescue treatment against lamivudine-resistant strains. The aim of this study was to assess the patterns of lamivudine-resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty-seven patients with lamivudine-resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine-resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real-time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%) rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M, rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was always observed in conjunction with rtM204I. Decrease in mean serum HBV did not differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (−3.3 vs. −3.3 log10 copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL80I mutant is co-selected with rtM204I as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine-resistant HBV mutations. J. Med. Virol. 81:417–424, 2009. © 2009 Wiley-Liss, Inc.