Lamivudine-resistant chronic hepatitis B: an observational study on adefovir in monotherapy or in combination with lamivudine

J Hepatol. 2008 Apr;48(4):540-7. doi: 10.1016/j.jhep.2007.12.018. Epub 2008 Jan 31.

Abstract

Background/aims: In lamivudine-resistant patients with chronic hepatitis B (CHB), we compared efficacy, predictive response factors and changes in viral mutants in two antiviral approaches with adefovir.

Methods: A prospective cohort study on therapy with adefovir alone (29 patients) or combined with ongoing lamivudine (23 patients) was performed.

Results: A virological response was achieved in 55% of patients treated with adefovir and in 83% of those treated with the combination (p>0.05). This response was directly related to the basal viral load (p<0.0001) and obtained in 10 patients with basal HBV-DNA<17,200 IU/ml using both strategies. In patients with a higher basal viral load, the virological response was more frequent when treated with the combination (p<0.05). Mutation at locus rt181 predicted HBV-DNA persistence during therapy. A virological rebound was observed in 18% of non-responders while on adefovir monotherapy.

Conclusions: To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine-resistant patients, rescue therapy is preferable at early evidence of genotypic resistance. However, in subjects with a significant viral load, combination therapy is more effective. The presence of the rt181 mutation is associated with incomplete response.

Publication types

  • Comparative Study

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / analysis
  • Drug Resistance, Multiple, Viral*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / therapeutic use*
  • Polymerase Chain Reaction
  • Prospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Adenine
  • adefovir dipivoxil