Human immunodeficiency virus (HIV) enters target cells by a process involving direct fusion between the virus and cell membranes. This process begins when the HIV envelope glycoprotein (Env) binds to CD4, the primary receptor on the target cell surface. It has long been recognized that CD4 alone is not sufficient to allow HIV entry; an additional “coreceptor” on the target cell is required. Evidence has suggested that the tropism of different HIV strains for infection of various target cell types (for example, T-cell lines, macrophages, primary T cells) results from the ability of the corresponding Envs to use distinct coreceptors, which in turn are differentially expressed on various CD4-positive target cell types.