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


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-->5 microM; ddC, < 0.01-0.23 microM; ddI, 0.2-->25 microM). Against both nucleoside susceptible and resistant isolates XM323 exhibited potent inhibition with IC50 values of < 0.02-0.27 microM and IC90 values of 0.03-1.17 microM.


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.
Winslow
D L
DL
DuPont Merck Pharmaceutical Company, Glenolden, Pennsylvania.
Mayers
D
D
Scarnati
H
H
Lane
J
J
Bincsik
A
A
Otto
M J
MJ
D000998:Antiviral Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D016049:Didanosine / Q000494:pharmacology; D015726:Giant Cells; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D001381:Azepines; D017320:HIV Protease Inhibitors; C085886:XM 323; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine