In vitro susceptibility of clinical isolates of HIV-1 to XM323, a non-peptidyl HIV protease inhibitor

Abstract

Objective To determine the in vitro susceptibility of primary clinical isolates and laboratory strains of HIV-1 to XM323. Methods The AIDS Clinical Trials Group/US Department of Defense p24 antigen-based consensus assay was used to determine in vitro susceptibility of 57 primary clinical isolates and three laboratory strains of HIV-1 to XM323, zidovudine, zalcitabine (ddC), and didanosine (ddl). Results The 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 IC₅₀ values of < 0.02–0.27 μM and IC₉₀ values of 0.03–1.17 μM. Conclusions XM323 is a potent inhibitor of diverse clinical isolates of HIV-1 in vitro and represents a novel class of non-peptidyl inhibitors of HIV-1 protease.