New approaches in the treatment of HIV/AIDS – focus on maraviroc and other CCR5 antagonists

Hans P Schlecht¹, Sarah Schellhorn², Bruce J Dezube³, Jeffrey M Jacobson¹

¹Department of Medicine (Infectious Diseases), Hahnemann University Hospital, Drexel University College of Medicine, Philadelphia, PA, USA; ²Department of Medicine, ³Department of Medicine (Hematology/Oncology), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Abstract: Treatment of HIV-1 infection has produced dramatic success for many patients. Nevertheless, viral resistance continues to limit the efficacy of currently available agents in many patients. The CCR5 antagonists are a new class of antiretroviral agents that target a necessary coreceptor for viral entry of many strains of HIV-1. Recently, the first agent within this class, maraviroc, was approved by a number of regulatory agencies, including the Food and Drug Administration. Herein we review the role of the CCR5 receptor in HIV-1 infection and potential methods to target it in anti-HIV-1 therapy. We review the various categories of agents and discuss specific agents that have progressed to clinical study. We discuss in detail the recently approved, first in class CCR5 antagonist, maraviroc, and discuss aspects of resistance to CCR5 antagonism and the potential role of CCR5 antagonism in the management of HIV-1 infection.

Keywords: CCR5, HIV-1 tropism, coreceptor, maraviroc, viral entry, chemokine receptor