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/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.


BACKGROUND
Clinicaltrials.gov identifier NCT00098748 .
Saag
Michael
M
School of Medicine, University of Alabama, Birmingham, AL 35294-2050, USA. msaag@uab.edu
Goodrich
James
J
Fätkenheuer
Gerd
G
Clotet
Bonaventura
B
Clumeck
Nathan
N
Sullivan
John
J
Westby
Mike
M
van der Ryst
Elna
E
Mayer
Howard
H
D000328:Adult; D000368:Aged; D003510:Cyclohexanes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006678:HIV / Q000235:genetics; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D018579:Patient Selection; D010641:Phenotype; D010919:Placebos; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D010919:Placebos; D014230:Triazoles; D000077592:Maraviroc