Service des maladies infectieuses et tropicales, CHU de Montpellier ; UMR 145 VIH et maladies associées, et Faculté de médecine, Université Montpellier 1, Hôpital Gui-de-Chauliac, 34295 Montpellier Cedex 5
CCR5 seems to be a promising target for inhibition of HIV-1 replication. Small-molecule chemokine receptor CCR5 antagonists are a new class of antiretrovirals that exert non competitive allosteric inhibition of the chemokine receptor CCR5, which is essential for HIV entry. The CCR5 antagonists aplaviroc (GlaxoSmithKline), vicriviroc (Schering-Plough), and maraviroc (Pfizer) have reached phases 2B and 3 of clinical development. The development of aplaviroc was stopped because of its hepatotoxicity in some infected patients. In ACTG 5211 or Motivate trials, treatment-experienced subjects who added vicriviroc or maraviroc demonstrated substantially greater reductions in plasma HIV-1 RNA levels than those who received the placebo. The place of this new class in the strategies of initial treatment or replacement remains to be clarified. The limitations of the use of these small molecules depend on their mechanism of action : need for monitoring the evolution of coreceptor usage, risk of failure by emergence of strains with CXCR4 tropism, potential risks due to blocking of the physiological functions of this chemokine receptor.