title: Maraviroc.
abstract: 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 300mg (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 300mg twice daily was well tolerated in treatment-experienced patients infected with R5-tropic HIV-1.
authors.affiliation: Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Carter
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Keating
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D000077592:Maraviroc; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc