IN-VITRO ANTI-HIV-1 ACTIVITY OF HIV PROTEASE INHIBITOR KNI-272 IN RESTING AND ACTIVATED CELLS - IMPLICATIONS FOR ITS COMBINED USE WITH AZT OR DDI

KNI-272, a conformationally constrained human immunodeficiency virus ( HIV) protease inhibitor containing a P1 allophenylnorstatine (Apns) (( 2S,3S)- 3-amino-2-hydroxy-4-phenylbutyric acid), has been shown to be a selective and potent inhibitor of the replication of a wide spectrum of HIV strains in vitro. When KNI-272 was tested in combination with 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine (ddI) ag ainst a primary HIV-1 isolate in phytohemagglutinin-activated peripher al blood mononuclear cells (PHA-PBM), its activity was identified to b e additive, but not synergistic or antagonistic, as analyzed with the COMBO program package. When tested alone for anti-HIV-1 activity in re sting PBM (R-PBM) and PHA-PBM, KNI-272 was found to be comparably pote nt against the virus in both target cell populations, whereas AZT was more potent in PHA-PBM than in R-PBM and ddI was more potent in R-PBM. These data suggest a potential clinical application of KNI-272 and it s analogs.