A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression

J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):290-7. doi: 10.1097/QAI.0b013e3181aa12d5.

Abstract

Background: Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression.

Methods: We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function.

Results: Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group.

Conclusions: In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Dideoxynucleosides / administration & dosage*
  • Dideoxynucleosides / adverse effects
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Lamivudine / administration & dosage*
  • Lamivudine / adverse effects
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage*
  • Organophosphonates / adverse effects
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects
  • Spain
  • Tenofovir
  • Treatment Failure
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Deoxycytidine
  • Lamivudine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • abacavir

Associated data

  • ISRCTN/ISRCTN61891868