INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN-VITRO BY COMBINATION OF DELAVIRDINE, ZIDOVUDINE AND DIDANOSINE

Delavirdine (DLV), a non-nucleoside reverse transcriptase inhibitor (R TI) of human immunodeficiency virus type 1 (HIV-1), was evaluated in t wo and three-drug combinations against acute and co-culture infections of HIV-1(JRCSF) in human peripheral blood mononuclear cells. DLV comb ined with didanosine (DDI) at 1:10 and 1:30 ratios were statistically synergistic (combination indices (CI)<1) at >75% inhibition levels. Ho wever, at 1:100 ratio, the interaction appeared to be additive. Three- drug combinations of zidovudine (ZDV), DLV, and DDI (at a ratio of 1:2 :333) were synergistic at 50-99% inhibition levels. The three-drug gro up also showed significantly (P < 0.01) lower p24 levels in acute cult ures than two-drug combination groups (DLV+ZDV, DLV+DDI, ZDV+DDI). In co-culture studies, the extent of viral inhibition was dependent on dr ug dose and the duration of treatment. Combination of DLV, ZDV, and DD I at IC95 concentration of the individual drugs showed complete inhibi tion of viral growth in co-culture after 19 days, but not after 7 or 1 2 days of treatment. The combinations studied did not show additive or synergistic drug toxicity. These data provide an in vitro basis for b eneficial use of DLV in combinations with DDI and ZDV in HIV-1 infecte d patients. (C) 1997 Elsevier Science B.V.