Human immunodeficiency virus (HIV) entry inhibitors (CCR5 specific blockers) in development: Are they the next novel therapies?

Since the introduction of the nucleoside reverse transcriptase inhibitor zidovudine in 1987, the number of the available antiretroviral medications has grown to about 20. Despite the efficacy of these medications, treatment-limiting adverse events are frequent. During the last several years, a new class of antiretroviral drugs often referred to as entry inhibitors, specifically the CCR5 blockers, have moved from the basic science laboratories and are now in the clinical phases of drug development. There are three agents in phase 2/3 development that inhibit viral entry by binding to CCR5, disrupting the interaction between the co-receptor and viral glycoprotein (gp) 120. They are aplaviroc (GW-873140), maraviroc (UK-427,857), and vicriviroc (SCH 417690). The development of these new antiviral agents that target different aspects of the viral life cycle is likely to make it possible to suppress viral strains that are resistant to the currently available antiretroviral drugs. There is a growing need for a new class of antiretrovirals with reduced toxicity and improved tolerability. However, currently available information suggests further pharmacokinetics, resistance, safety, and efficacy data are needed to understand how these agents may be effectively used in the clinical setting.