HIV entry inhibitors in clinical development

Despite recent advances, present therapies for human immunodeficiency virus type 1 (HIV-1) infection are limited by their failure to eradicate HIV-1, by the emergence of multidrug-resistant variants and by significant toxicities. Current therapies collectively target two viral enzymes involved in intracellular viral replication processes, and there is an urgent need for new treatment modalities. HIV-1 entry is a multistep process that comprises viral attachment, co-receptor interactions and fusion. This cascade of events offers opportunities for therapeutic intervention, and clinical proof-of-principle has been obtained for inhibitors of each step. These agents are referred to broadly as entry inhibitors.