A RANDOMIZED, CONTROLLED, DOUBLE-BLIND-STUDY COMPARING THE SURVIVAL BENEFIT OF 4 DIFFERENT REVERSE-TRANSCRIPTASE INHIBITOR THERAPIES (3-DRUG, 2-DRUG, AND ALTERNATING DRUG) FOR THE TREATMENT OF ADVANCED AIDS

Objective: The primary objective was to compare the effects of dual or triple combinations of HN-I reverse transcriptase inhibitors with res pect to survival. The time to new HIV disease progression or death, to xicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated. Design: This was a mult icenter randomized, double-blind: placebo-controlled study. Setting: T he study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers. Patients: 1313 HIV-infe cted patients with CD4 counts less than or equal to 50 cells/mm(3) par ticipated in this study, which was conducted from June 1993 to June 19 96. Intervention: Patients were randomized to one of four daily regime ns containing 600 mg of zidovudine: zidovudine alternating monthly wit h 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudin e plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine p lus 400 mg of nevirapine (triple therapy). Main Outcome Measures: The main outcome was survival (i.e., time to death). Results: A significan t difference in survival time was found between the four treatment gro ups, favoring those assigned to triple therapy (p = .02). A significan t difference was also found in the delay of disease progression or dea th among the four treatment arms favoring the group assigned to triple therapy(p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA conc entrations as well as changes of CD4 counts at week 8 predicted surviv al for subjects in the virology substudy. Conclusions: In the pre-prot ease inhibitor era, a combination of triple reverse transcriptase inhi bitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression.