SYNERGISTIC INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN-VITRO BY 2-DRUG AND 3-DRUG COMBINATIONS OF DELAVIRDINE, LAMIVUDINE AND ZIDOVUDINE

Delavirdine (DLV), a non-nucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, was evaluated in two- and t hree-drug combination regimens with lamivudine (3TC) and zidovudine (Z DV). The effect of continuous drug treatment on HIV-1(JR-CSF) replicat ion in human peripheral blood mononuclear cells was measured by an ELI SA for p24 core antigen. Drug synergy, estimated by the combination in dex method and the method of Pritchard & Shipman, was observed when DL V was combined with 3TC over a range of drug concentrations (DLV at 1, 3, 10, 30 and 100 nM; 3TC at 3, 10, 30, 100 and 300 nM). Two-drug com binations of ZDV and DLV at a 1.3 ratio or ZDV and 3TC at a 1:10 ratio were synergistic at greater than 75% inhibition levels. Three-drug co mbinations of ZDV, DLV and 3TC (ZDV at 0.3, 1, 3 and 10 nM; DLV at 1, 3, 10 and 30 nM; 3TC at 3, 10, 30 and 100 nM) at the ratio of 1:3:10 a lso yielded significant synergistic effects. None of the combinations studied showed significant additive or synergistic drug toxicity. Thes e in vitro data suggest that DLV should be evaluated in two- and three -drug combinations with 3TC and ZDV in clinical trials.