LAMIVUDINE OR STAVUDINE IN 2-DRUG AND 3-DRUG COMBINATIONS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN-VITRO

Two- and three-drug combinations of lamivudine or stavudine with other antiretroviral drugs were evaluated for activity against human immuno deficiency virus type 1 (HIV-1) activity in peripheral blood mononucle ar cells, Other agents included zidovudine, didanosine, nevirapine, an d saquinavir. Paired zidovudine-sensitive and -resistant clinical HIV- 1 isolates were used, Additive or synergistic interactions were observ ed against the zidovudine-sensitive isolate with the following combina tions: lamivudine-zidovudine, lamivudine-stavudine, lamivudine-saquina vir, lamivudine-nevirapine, stavudine-zidovudine, stavudine-didanosine , stavudine-saquinavir, stavudine-nevirapine, lamivudine-zidovudine-sa quinavir, lamivudine-zidovudine-stavudine, stavudine-zidovudine-nevira pine, lamivudine-zidovudine-nevirapine, and stavudine-zidovudine-saqui navir. Against the zidovudine-resistant isolate, additive or synergist ic interactions were seen with most two- and three-drug combinations, but the combination of stavudine-zidovudine was antagonistic, The clin ical implications of these in vitro observations should be explored.