A Study to Compare the Effectiveness of Different Anti-HIV Drug Regimens in Keeping Levels of HIV in the Blood as Low as Possible

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.