This was a Phase II, randomized, partially double-blinded trial to determine the influence of the longitudinal immunologic and virologic profiles of HIV-infected individuals with well defined combination nucleoside analog exposure on the response to newly introduced antiretroviral interventions. Subjects were randomized to one of three treatment arms in a partially- blinded fashion (open-label ZDV was provided) and followed for 48 weeks: Arm A: ZDV 200 mg t.i.d./ddI 200 mg b.i.d. plus 3TC placebo b.i.d. or ZDV 200 mg t.i.d./ddC 0.75 mg t.i.d. plus 3TC placebo b.i.d. Arm B: ZDV 200 mg t.i.d./ddI 200 mg b.i.d. plus 3TC 150 mg b.i.d. or ZDV 200 mg t.i.d./ddC 0.75 mg t.i.d. plus 3TC 150 mg b.i.d. Arm C: ZDV 200 mg t.i.d./ddI placebo b.i.d. plus 3TC 150 mg b.i.d. or ZDV 200 mg t.i.d./ddC placebo t.i.d. plus 3TC 150 mg b.i.d. The primary goals outlined in this trial were to characterize subjects who had a well defined nucleoside exposure history to determine the influence of vial load, CD4+ counts, biologic phenotype and the presence of symptomatic HIV disease on the response to a new therapy, on the rate of emergence of the 3TC associated resistance mutation at codon 184, and on the kinetics of viral replication in HIV infected patients who had been treated with either monotherapy (ZDV or ddI) or dual combination therapy (ZDV/ddI or ZDV/ddC) while participating in ACTG 175. The practical question of the potential utility of 3TC, either as part of a three drug regimen or in combination with ZDV was explored. There were 325 patients enrolled nationwide following closure to enrollment on January 12, 1996. Subjects were unblinded to their assigned treatment regimen beginning 21 February 1997. Those subjects who were on treatment/on study at the time of unblinded were allowed to continue on the open-label extension until July 14, 1997 when ACTG 364 (a rollover protocol for ACTG 303) was approved for implementation. ACTG 364 is designed to compare the virologic efficacy of Nelfinavir and/or DMP-266 in combination with one or two new nucleoside analogs in nucleoside experienced subjects.