A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1.

Academic Article

Abstract

  • BACKGROUND: Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual- or mixed-tropic strains of human immunodeficiency virus type 1 (HIV-1). A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1. METHODS: Treatment-experienced patients with an HIV-1 RNA level 5000 copies/mL who had received 3 classes of drugs and/or were infected with virus resistant to 2 drug classes and were infected with non-R5 HIV-1 were randomized to receive optimized background therapy plus maraviroc (once or twice daily) or placebo. The primary end point was change in HIV-1 RNA level from baseline to 24 weeks. RESULTS: Among 167 patients infected with dual- or mixed-tropic HIV-1, baseline mean HIV-1 RNA levels were >5 log(10) copies/mL and median CD4(+) cell counts were <50 cells/microL. From baseline to 24 weeks, patients who received placebo demonstrated a mean decrease in HIV-1 RNA levels of 0.97 log(10) copies/mL, compared with mean decreases of 0.91 and 1.20 log(10) copies/mL for those who received maraviroc once (P =.83) or twice (P +.38) daily, respectively. Mean increases in CD4(+) cell counts from baseline were 36 cells/microL for patients who received placebo, 60 cells/microL among patients who received maraviroc once daily, and 62 cells/microL among patients who received maraviroc twice daily. The incidences of serious adverse events were similar among groups. CONCLUSIONS: In this exploratory study involving extensively treatment-experienced patients with advanced, non-R5 HIV-1 infection, neither superiority nor noninferiority was statistically demonstrated for either maraviroc dosage compared with placebo at 24 weeks of treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00098748 .
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    Keywords

  • Adult, Aged, Cyclohexanes, Double-Blind Method, Female, Genotype, HIV, HIV Fusion Inhibitors, HIV Infections, Humans, Least-Squares Analysis, Male, Maraviroc, Middle Aged, Patient Selection, Phenotype, Placebos, Triazoles, Viral Load, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Saag M; Goodrich J; F√§tkenheuer G; Clotet B; Clumeck N; Sullivan J; Westby M; van der Ryst E; Mayer H; A4001029 Study Group
  • Start Page

  • 1638
  • End Page

  • 1647
  • Volume

  • 199
  • Issue

  • 11