Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection

J Infect Dis. 2010 Mar 15;201(6):803-13. doi: 10.1086/650697.

Abstract

Background: The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection.

Methods: Patients screened for R5 HIV-1 were randomized to receive efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with zidovudine-lamivudine. Coprimary end points were proportions of patients with a viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was assessed.

Results: The once-daily maraviroc arm was discontinued for not meeting prespecified noninferiority criteria. In the primary 48-week analysis (n = 721), maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of -10%. More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis excluding 107 patients (15%) with non-R5 screening virus by the current, more sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval for the difference between treatment groups was above -10% for each end point.

Conclusions: Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) .

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / standards
  • Anti-Retroviral Agents
  • Antiviral Agents / pharmacology
  • Benzoxazines / pharmacology
  • Benzoxazines / standards
  • Benzoxazines / therapeutic use*
  • CCR5 Receptor Antagonists*
  • Cyclohexanes / pharmacology
  • Cyclohexanes / standards
  • Cyclohexanes / therapeutic use*
  • Cyclopropanes
  • Double-Blind Method
  • Drug Combinations
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Lamivudine / administration & dosage
  • Male
  • Maraviroc
  • Middle Aged
  • Receptors, CCR5 / metabolism
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / standards
  • Triazoles / therapeutic use*
  • Viral Load
  • Viral Tropism
  • Young Adult
  • Zidovudine / administration & dosage

Substances

  • Alkynes
  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Antiviral Agents
  • Benzoxazines
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Cyclopropanes
  • Drug Combinations
  • Receptors, CCR5
  • Triazoles
  • Lamivudine
  • Zidovudine
  • efavirenz
  • Maraviroc

Associated data

  • ClinicalTrials.gov/NCT00098293