IN-VITRO INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY A COMBINATION OF DELAVIRDINE (U-90152) WITH PROTEASE INHIBITOR U-75875 OR INTERFERON-ALPHA

Delavirdine (bisheteroarylpiperazine, U-90152), a nonnucleoside revers e transcriptase inhibitor of human immunodeficiency virus type 1 (HIV- 1), was evaluated in a two-drug combination with recombinant human int erferon-alpha (IFN-alpha) or the peptidomimetic protease inhibitor U-7 5875 against HIV-1 replication in vitro. Viral growth was assayed in a CD4(+) T cell line (H9) infected with HIVIIIB and in human peripheral blood mononuclear cells infected with the clinical isolate HIVJRCSF. Drug synergy, estimated by the combination index method and the method of Pritchard and Shipman, was observed when delavirdine was combined with U-75875 or IFN-alpha over a range of drug concentrations (delavir dine: 0.001, 0.003, 0.01, 0.03 mu M; U-75875: 0.01, 0.03, 0.1, 0.3, 1. 0 mu M; IFN-alpha: 2, 6, 17, and 50 or 10, 30, 100, and 300 IU/mL). Th e combinations showed no detectable drug antagonism or cytotoxicity. T hese in vitro synergy data support the potential use of delavirdine wi th either a protease inhibitor or IFN-alpha in patients with AIDS.