Extended treatment with lamivudine and adefovir dipivoxil in chronic hepatitis B patients with lamivudine resistance

Robert P. Perrillo, Hie Won Hann, Eugene Schiff, David Mutimer, Bernard Willems, Nancy Leung, William M. Lee, Susan Dixon, Mary Woessner, Carol L. Brosgart, Lynn D. Condreay, Stephen D. Gardner

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Purpose: We and others have reported that adding adefovir dipivoxil (adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV. Methods: A total of 78 patients with compensated CHB (Group A) were maintained on either adefovir 10 mg daily (n = 38) or placebo (n = 40) while continuing lamivudine. An additional 38 patients with decompensated cirrhosis or post liver transplantation (Group B) received lamivudine plus adefovir. The primary endpoint was HBV DNA response at year 2. Results: At week 104 of therapy, a significantly greater proportion of patients in Group A on combination therapy (76%) had a decline in serum HBV DNA to 105 copies or >2 log10 reduction from baseline compared to those receiving lamivudine alone (13%; p < 0.001). Fifty-two percent of Group A patients on combination treatment continued to have the M204V/I HBV mutation compared to 92% receiving lamivudine alone (p = 0.0013). Virologic response occurred less frequently in patients expressing persistent lamivudine resistant HBV. In Group B, 87% of patients had HBV DNA response at week 104 (median change from baseline of -5.84 log10 copies/mL). Conclusions: The combination of lamivudine and adefovir for 2 years generally proved effective in lamivudine-resistant cases, but there was a persistently high rate of detection of lamivudine resistant mutants and impaired virologic response in compensated patients.

Original languageEnglish (US)
Pages (from-to)654-663
Number of pages10
JournalHepatology International
Volume5
Issue number2
DOIs
StatePublished - Jun 2011

Keywords

  • Adefovir dipivoxil
  • Chronic hepatitis B
  • Combination therapy
  • Lamivudine
  • Resistance

ASJC Scopus subject areas

  • Hepatology

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    Perrillo, R. P., Hann, H. W., Schiff, E., Mutimer, D., Willems, B., Leung, N., Lee, W. M., Dixon, S., Woessner, M., Brosgart, C. L., Condreay, L. D., & Gardner, S. D. (2011). Extended treatment with lamivudine and adefovir dipivoxil in chronic hepatitis B patients with lamivudine resistance. Hepatology International, 5(2), 654-663. https://doi.org/10.1007/s12072-010-9228-9