Antagonistes du récepteur CCR5 et infection par le VIH-1 : bases et conséquences de cette approche thérapeutique

CCR5 molecule is a chemokine receptor with an important role in infectious diseases; not only is it the main coreceptor for HIV-1, but it has also been involved in the immune defense against various transmissible agents. CCR5 antagonists constitute a new class of antiretrovirals. Three molecules of this class have reached phases 2B and 3 of clinical development: aplaviroc (GlaxoSmithKine), vicriviroc (Schering-Plough) and maraviroc (Pfizer). The development of aplaviroc was stopped because of some cases of drug-induced hepatitis. In ACTG 5211 and Motivate trials, adding vicriviroc (in phase 3 trials) or maraviroc (now approved for clinical use) respectively to an optimized background regimen in treatment-experienced patients has resulted in a significant virologic benefit. The place of this new therapeutic class in strategies of initial, switch or rescue treatment needs further investigation, and its interest in immunological non-responders, in severe immunosuppressed patients or in subjects harbouring non-R5 HIV-1 strains, remains to be addressed. Major concerns about their use still remain, including long-term tolerability, the risk of inducing an R5 to X4 switch, particularly in compartments other than blood, and the risk of interfering with some immune responses.