Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure

Hepatol Int. 2016 Sep;10(5):779-88. doi: 10.1007/s12072-016-9737-2. Epub 2016 May 20.

Abstract

Background and aims: In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen.

Methods: In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks.

Results: At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed.

Conclusions: In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

Keywords: Antiviral resistance; Multidrug failure; Partial response; Primary non-response; Rescue therapy; Virologic breakthrough.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • DNA, Viral / blood
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Tenofovir / administration & dosage*
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • entecavir
  • Guanine
  • Tenofovir