Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection

N Engl J Med. 2004 Apr 29;350(18):1850-61. doi: 10.1056/NEJMoa031772.

Abstract

Background: Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.

Methods: This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.

Results: We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.

Conclusions: In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alkynes
  • Benzoxazines
  • CD4 Lymphocyte Count
  • Cyclopropanes
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use
  • Double-Blind Method
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV-1* / genetics
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Nucleosides / therapeutic use*
  • Oxazines / adverse effects
  • Oxazines / therapeutic use*
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides
  • Nucleosides
  • Oxazines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Zidovudine
  • efavirenz
  • abacavir

Grant support