Dynamics of lamivudine-resistant hepatitis B virus during adefovir monotherapy versus lamivudine plus adefovir combination therapy

Samreen Ijaz, Catherine Arnold, Samir Dervisevic, Jana Mechurova, Nick Tatman, Richard S. Tedder, Nikolai V. Naoumov

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Adefovir dipivoxil has been used alone or together with lamivudine to suppress lamivudine-resistant hepatitis B virus (HBV). However, the dynamics of HBV populations under different selection pressures and their impact on treatment outcome are poorly understood. Pyrosequencing® was applied to quantify longitudinally the evolution of wild type and lamivudine/adefovir- resistant HBV. Eight patients, with lamivudine-resistant HBV, were randomized to receive adefovir monotherapy or adefovir/lamivudine combination therapy for a median of 79 and 71 weeks, respectively. Pyrosequencing® proved highly sensitive with a lower limit of quantitation of minor HBV populations of 2% irrespective of viraemia levels. Adefovir/lamivudine treatment resulted in greater viraemia reduction than adefovir monotherapy. During combination therapy, lamivudine-resistant HBV populations (codons 180 and 204) remained dominant (>90%) and no adefovir-resistance developed. During adefovir monotherapy, reversion to wild-type HBV was detected in two patients with one patient accumulating rapidly adefovir-resistant HBV along with increased viraemia. In conclusion, the dynamics of drug-resistant HBV strains vary under different selection pressures which have a significant impact on the success of rescue therapy, as well as for the selection of new mutations. The use of techniques such as Pyrose-quencing provides an evidence-based approach for successful management of drug-resistant HBV.

Original languageEnglish
Pages (from-to)1160-1170
Number of pages11
JournalJournal of Medical Virology
Volume80
Issue number7
DOIs
Publication statusPublished - Jul 2008

Keywords

  • Adefovir resistance
  • HBV populations
  • Pyrosequencing
  • Rescue therapy

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