CD4 and infection: Determinants that modulate R5 macrophage infection have been mapped to residues within or proximal to the CD4 binding site on gp120 of the HIV-1 envelope glycoprotein (Env) [11,26,27] as well as in the variable V1 [28], V2 and [29] V3 loops [26] at the apex of the trimer [30].