This study compared antiretroviral activity among 6 "salvage" therapy regimens. The study was a prospective, randomized, 2x3 factorial, multicenter study of the AIDS Clinical Trials Group. The study enrolled 277 human immunodeficiency virus (HIV)-infected patients naive to nonnucleoside analogues who had taken indinavir >6 months. The patients had 2000-200,000 HIV RNA copies/mL. Patients received saquinavir with ritonavir or nelfinavir together with delavirdine and/or adefovir and were followed for safety and antiretroviral response between baseline and week 16. At week 16, 30% (77/254) of patients had </=500 HIV RNA copies/mL. Virologic response did not differ significantly between pooled ritonavir and nelfinavir groups (28% vs. 33%; P=.50) or between pooled delavirdine and delavirdine/adefovir groups (40% vs. 33%; P=.42). Pooled delavirdine groups had a greater virologic response rate than did adefovir groups (40% vs. 18%; P=.002). Overall, one-third of patients who experienced virologic failure on an indinavir-containing regimen suppressed virus load levels while they were taking a new salvage regimen.