HIV-1 cell entry and advances in viral entry inhibitor therapy

Despite the considerable successes of highly active antiretroviral therapy, new classes of therapeutic agents are still urgently needed. Unfortunately, the emergence of antiviral resistance and drug toxicity remain challenging obstacles to successful treatment in many HIV-1-infected individuals. HIV-1 entry is a multi-step process that is an attractive target for the development of new classes of therapeutic agents. Considerable progress has been made in the understanding of HIV-1 cell entry, enabling the design of specific agents that can inhibit each step of cellular entry. A number of promising agents have commenced clinical trials, including the attachment inhibitor PRO 542, co-receptor inhibitor AMD3100 and fusion inhibitor T-20. A greater number of HIV-1 entry inhibitors are in preclinical development. This review outlines the mechanisms involved in HIV-1 entry and the sites of action of specific HIV-1 inhibitors.