THE DEVELOPMENT OF A RATIONAL ANTIRETROVIRAL THERAPY FOR AIDS

Current information indicates that world-wíde, through June 1992, 2.5 million people have died of AIDS, 160,000 in the United States alone. Especially alarming is the spread of the epidemic in sorne of the poorest countries of the Third world. Efforts made since 1983 to understand the molecular, cellular and clínica! features of HIV-1 infection, the causative agent of AIDS in humans, have facilitated elaboration of estrategíes for therapeutic intervention. The in vitro activity of 3' - azido - 3' - deoxythymidine (AZT, zidovudíne) against HIV-1, via the (viral) encoded reverse transcriptase (RT), established the enzyme as a major target for antiviral therapy, followed by the demonstration of the effectiveness of 2' ,3-dideoxynucleosides, in general, as potent inhibitors of HIV-1. Subsequent clinical tria Is led to the approval of zidovudine and then 2',3'-dideoxyinosine (ddl, didanosine) for treatment of AIDS. Recently, the combination of zidovudine and 2',3'dideoxycytidine (ddC zalcitabine), which exhibits different toxicity profiles, was granted I imited approval for treatment of advanced HIV-1 infection.