Maraviroc is a specific, slowly reversible, noncompetitive, small-molecule antagonist of the CCR5 chemokine receptor, which also serves as an HIV-1 coreceptor. By acting as an antagonist at the CCR5 coreceptor, maraviroc inhibits HIV-1 from entering host cells. Clinical data for maraviroc are available from two large, well designed, ongoing phase IIb/III trials (MOTIVATE-1 and MOTIVATE-2) conducted in patients infected with R5-tropic HIV-1 who had previously received at least one agent from three of the four classes of antiretroviral drugs and/or were triple-class resistant. According to 24-week interim results of the MOTIVATE-1 and -2 trials, a significantly greater reduction in viral load occurred in patients receiving maraviroc 150 or 300 mg (depending on optimised background therapy [OBT]) twice daily plus OBT compared with placebo plus OBT. This significant difference was maintained at 48 weeks in MOTIVATE-1. In the MOTIVATE-1 and -2 trials, a significantly greater proportion of patients receiving maraviroc plus OBT achieved an HIV-1 RNA level <400 and <50 copies/mL compared with those receiving placebo plus OBT. In addition, the CD4+ cell count was increased to a significantly greater extent with maraviroc plus OBT compared with placebo plus OBT. The 48-week results of MOTIVATE-1 also report a significant difference in favour of maraviroc for all these endpoints. In general, maraviroc at dosages of up to 300 mg twice daily was well tolerated in treatment-experienced patients infected with R5-tropic HIV-1.
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