Efficacy of Tenofovir-based Rescue Therapy in Lamivudine-resistant Chronic Hepatitis B Patients With Failure of Lamivudine and Adefovir Combination

Clin Ther. 2015 Jul 1;37(7):1433-42. doi: 10.1016/j.clinthera.2015.04.007. Epub 2015 May 5.

Abstract

Purpose: In chronic hepatitis B patients, lamivudine (LAM) and adefovir (ADV) combination therapy is commonly used as a rescue therapy for LAM resistance, but it often results in incomplete viral suppression. We investigated the antiviral efficacy of tenofovir (TDF)/LAM combination therapy versus TDF monotherapy in LAM-resistant chronic hepatitis B (CHB) patients who failed to respond to LAM plus ADV rescue therapy.

Methods: Among 108 patients with LAM-resistant CHB who had a partial virologic response (VR) to LAM and ADV combination therapy, Eighty one patients were finally included in this study.

Findings: Resistance to ADV (ADV-R) was present in 32 patients (39.5%), and the remaining 49 patients (60.5%) had a partial virologic response to LAM/ADV combination (ADV-P). The study subjects were treated with TDF alone (n=15) or TDF/LAM combination (n=66). VR was achieved in 61 patients (75.3%). The rates of VR at 6 and 12 months were not significantly different between TDF monotherapy and TDF/LAM combination therapy groups (46.7 vs. 68.2% at 6 months, and 66.7 vs. 75.9% at 12 months, log-rank P=0.357). Treatment efficacy of TDF alone or TDF/LAM combination was not statistically different according to pre-existing ADV or LAM resistant strains. In multivariate analysis, absolute HBV DNA levels at the start of TDF rescue treatment (P<0.001; OR, 0.556; 95% CI, 0.422-0.731) were the only significantly associated with VR.

Implications: TDF monotherapy was as effective as TDF/LAM combination therapy in maintaining viral suppression in patients with LAM-resistant patients who failed to respond to LAM/ADV combination therapy.

Keywords: adefovir resistance; chronic hepatitis B; lamivudine resistance; tenofovir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / administration & dosage
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Retreatment
  • Tenofovir / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Organophosphonates
  • Lamivudine
  • adefovir
  • Tenofovir
  • Adenine