Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients

J Antimicrob Chemother. 2009 Jun;63(6):1087-96. doi: 10.1093/jac/dkp113. Epub 2009 Apr 18.

Abstract

Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

MeSH terms

  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Cyclohexanes / adverse effects
  • Cyclohexanes / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • Humans
  • Maraviroc
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • Triazoles
  • Maraviroc