ObjectiveTo determine thein vitrosusceptibility of primary clinical isolates and laboratory strains of HIV-1 to XM323.MethodsThe AIDS Clinical Trials Group/US Department of Defense p24 antigen-based consensus assay was used to determinein vitrosusceptibility of 57 primary clinical isolates and three laboratory strains of HIV-1 to XM323, zidovudine, zalcitabine (ddC), and didanosine (ddl).ResultsThe concentrations of compound required to inhibit viral p24 antigen production by 50% [median inhibitory concentration (IC50)] for nucleosides were as follows: zidovudine, 0.001->5μM; ddC, < 0.01–0.23μM; ddl, 0.2-25μM). Against both nucleoside susceptible and resistant isolates XM323 exhibited potent inhibition with IC50values of < 0.02–0.27 μM and IC90values of 0.03–1.17 μM.ConclusionsXM323 is a potent inhibitor of diverse clinical isolates of HIV-1in vitroand represents a novel class of non-peptidyl inhibitors of HIV-1 protease.