Objective:The primary objective was to compare the effects of dual or triple combinations of HIV-1 reverse transcriptase inhibitors with respect to survival. The time to new HIV disease progression or death, toxicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated.
Design:This was a multicenter randomized, double-blind, placebo-controlled study.
Setting:The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers.
Patients:1313 HIV-infected patients with CD4 counts ≤50 cells/mm3 participated in this study, which was conducted from June 1993 to June 1996.
Intervention:Patients were randomized to one of four daily regimens containing 600 mg of zidovudine: zidovudine alternating monthly with 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudine plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine plus 400 mg of nevirapine (triple therapy).
Main Outcome Measures:The main outcome was survival (i.e., time to death).
Results:A significant difference in survival time was found between the four treatment groups, favoring those assigned to triple therapy (p = .02). A significant difference was also found in the delay of disease progression or death among the four treatment arms favoring the group assigned to triple therapy (p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA concentrations as well as changes of CD4 counts at week 8 predicted survival for subjects in the virology substudy.
Conclusions:In the pre-protease inhibitor era, a combination of triple reverse transcriptase inhibitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression.
Address correspondence and reprint requests to Keith Henry, HIV Program, Regions Hospital, 640 Jackson, Suite 125, St. Paul, MN 55101, U.S.A.; email: firstname.lastname@example.org.
Manuscript received March 24, 1998; accepted June 17, 1998.
© 1998 Lippincott Williams & Wilkins, Inc.