A Double-Blind, Placebo-Controlled Trial of Maraviroc in Treatment-Experienced Patients Infected with Non-R5 HIV-1

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/mu L. 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/mu L for patients who received placebo, 60 cells/mu L among patients who received maraviroc once daily, and 62 cells/mu L 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.