To maximize the likelihood of a favorable response to salvage therapy, 4 or 5 drug regimens should be studied. Regimens containing fewer drugs, particularly those lacking a non-nucleoside reverse transcriptase inhibitor (NNRTI) such as efavirenz, are likely to result in an unacceptable rate of virological failure. Therefore, this study examines drug combinations which include two new nucleoside reverse transcriptase inhibitors (NRTIs), the NNRTI efavirenz, and either one or two protease inhibitors which are known not to produce cross-resistance to nelfinavir.

Patients are randomly selected to receive 1 of the following 4 treatment regimens:

Arm A: Ritonavir, saquinavir, efavirenz, and 2 new NRTIs. Arm B: Indinavir, efavirenz and 2 new NRTIs. Arm C: Amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 3/22/00: Patients have the option to increase the APV dose or to add low-dose ritonavir. APV will continue to be provided by the study; ritonavir will not be provided by the study.] Arm D: Indinavir, amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 6/28/99: All treatment regimens must include at least 1 new NRTI.] [AS PER AMENDMENT 3/22/00: ACTG 400 will continue to provide originally randomized study medications to all patients until approximately May 10, 2000, regardless of virologic response. Patients may also add antiretrovirals of their choice to this regimen (not provided by the study).] Clinical assessments are taken at Weeks 2, 4, 8, 12, 16, and every 8 weeks thereafter for the duration of the study. In addition, 2 substudies are being conducted: a drug-interaction substudy and a drug-exposure substudy. [AS PER AMENDMENT 3/22/00: Both substudies are closed to accrual and their pharmacokinetics assessments are discontinued.]