Virologic response and resistance to adefovir in patients with chronic hepatitis B

J Hepatol. 2006 Feb;44(2):283-90. doi: 10.1016/j.jhep.2005.10.018. Epub 2005 Nov 15.

Abstract

Background: The incidence and risk factors for adefovir-resistant HBV have not been clearly defined.

Aims: To characterize the virologic response to adefovir, to determine the rate of adefovir resistance and to explore factors associated with initial virologic response (IVR) and adefovir resistance.

Methods: All hepatitis B patients who received adefovir for > or =6 months at our center were prospectively monitored for virologic response and adefovir resistance.

Results: Forty three patients were included; mean treatment duration was 18 months (range 6-45). Thirty four (79%) patients had prior lamivudine. IVR was observed in 44% patients and associated with higher pretreatment ALT (P = 0.05) and the absence of HBeAg (P = 0.02). Six (14%) patients were found to have adefovir-resistant mutations. The cumulative probability of genotypic resistance to adefovir at month 24 was 22%. Patients with adefovir resistance were more likely to have been switched from lamivudine to adefovir monotherapy (P = 0.01), to be older (P = 0.04), and to be infected with HBV genotype D (P = 0.02).

Conclusions: Roughly 50% of patients failed to achieve IVR on adefovir. The cumulative probability of adefovir resistance at 2 years was 22%. Our data suggest that combination of lamivudine and adefovir may prevent emergence of adefovir resistance in patients with lamivudine-resistant HBV.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / genetics*
  • Drug Resistance, Viral / genetics*
  • 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
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Lamivudine
  • adefovir
  • Adenine