Class-sparing regimens for initial treatment of HIV-1 infection

N Engl J Med. 2008 May 15;358(20):2095-106. doi: 10.1056/NEJMoa074609.

Abstract

Background: The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.

Methods: In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.

Results: At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.

Conclusions: Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Benzoxazines / adverse effects
  • Benzoxazines / therapeutic use*
  • Cyclopropanes
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Humans
  • Kaplan-Meier Estimate
  • Lopinavir
  • Male
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use*
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use*
  • Treatment Failure

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • HIV Protease Inhibitors
  • Pyrimidinones
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • efavirenz
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00050895

Grants and funding