Virological response to adefovir monotherapy and the risk of adefovir resistance

World J Gastroenterol. 2011 Aug 14;17(30):3526-30. doi: 10.3748/wjg.v17.i30.3526.

Abstract

Aim: To evaluate virological response to adefovir (ADV) monotherapy and emergence of ADV-resistant mutations in lamivudine (LAM)-resistant chronic hepatitis B patients.

Methods: Seventy-seven patients with documented LAM resistance who were treated with 10 mg/d ADV for > 96 wk were analyzed for ADV resistance.

Results: At week 48 and 96, eight (10%) and 14 (18%) of 77 LAM-resistant patients developed the ADV-resistant strain (rtA181V/T and/or rtN236T mutations), respectively. Hepatitis B virus (HBV) DNA levels during therapy were significantly higher in patients who developed ADV resistance than in those who did not. Incidence of ADV resistance at week 96 was 11%, 8% and 6% among patients with complete virological response (HBV DNA level < 60 IU/mL); 0%, 5% and 19% among patients with partial virological response (HBV DNA level ≥ 60 to 2000 IU/mL); and 32%, 34% and 33% among patients with inadequate virological response (HBV DNA levels > 2000 IU/mL) at week 12, week 24 and week 48, respectively. HBV DNA levels > 2000 IU/mL at week 24 showed best performance characteristics in predicting ADV resistance.

Conclusion: Development of ADV resistance mutations was associated with HBV DNA levels, which could identify patients with LAM resistance who are likely to respond to ADV monotherapy.

Keywords: Adefovir; Drug resistance; Hepatitis B virus; Lamivudine; Viral DNA.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Drug Resistance, Viral / physiology*
  • Female
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / pharmacology*
  • Organophosphonates / therapeutic use*
  • Retrospective Studies

Substances

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