Combination antiretroviral therapies using protease inhibitors (PIs) are capable of suppressing plasma HIV RNA to undetectable levels. However, approximately 10% of patients who achieve undetectable viral loads will experience a detectable rise in HIV RNA each year. When HIV replication has been suppressed to very low levels, it may be possible to consolidate antiretroviral therapy into a simpler and potentially less toxic "maintenance" regimen without a PI. Such a regimen would ideally be potent enough to continue to maintain viral suppression but use agents that are better tolerated, more easily salvaged, less expensive, and/or more convenient than PI-containing regimens. Subsequent rises in HIV viremia with non-PI maintenance regimens may respond to resumption of the pre-maintenance PI-containing regimen, extending the use of the potent PI class.

Patients are randomized 1:1:1 to treatment with ddI/d4T/HU (Arm A) versus ddI/d4T/EFV (Arm B) versus continuation of the pre-entry PI-containing regimen (Arm C). Viral load is measured at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, then every 8 weeks for up to 3 years. Upon virologic failure (plasma HIV RNA greater than or equal to 200 copies/ml), or drug intolerance, patients on the maintenance regimens (Arms A and B) restart their pre-entry PI-containing regimen. Patients on Arm C are managed according to best medical judgment of their primary care provider in the event of virologic failure.

Inclusion Criteria

You may be eligible for this study if you:

• Are at least 13 years old (need consent if under 18).
• Are HIV-positive.
• Are taking your first anti-HIV drug regimen, which must include a PI and at least one NRTI (nucleoside reverse transcriptase inhibitor) and have been on this regimen for at least 12 months.
• Have a viral load less than 400 copies/ml for at least 12 months prior to study entry, and have a viral load less than 50 copies/ml within 60 days of study entry.
• Have a CD4 cell count of at least 200 cells/mm3 within 60 days of study entry.
• Are willing to go back on the drugs you are currently on, if necessary.
• Are willing to use effective methods of birth control during the study and for 3 months after.

Exclusion Criteria

You will not be eligible for this study if you:

• Have taken ddI, d4T, or HU for more than 2 weeks.
• Have taken any NNRTI (non-nucleoside reverse transcriptase inhibitor) for more than 7 days.
• Have ever taken EFV.
• Have received an HIV vaccine within 30 days prior to study entry.
• Have an AIDS-related cancer that requires chemotherapy.
• Have or have had pancreatic disease.
• Are being treated for a significant illness.
• Abuse drugs or alcohol.
• Are pregnant or breast-feeding.
• Are allergic to any study drugs.
• Have received certain medications.