Successful therapy following viral rebound has been problematic. Intensification of the existing regimen by adding 1 or 2 drugs generally has been avoided. However, successfully adding new drugs to an existing regimen would be advantageous since it would expose the patient to fewer antiretroviral agents in the overall treatment course. Recent evidence suggests that a significant proportion of patients who experience viral rebound while receiving a protease inhibitor (PI) actually have viral rebound with a PI-sensitive virus. Other studies have shown that treatment decisions based on resistance assays result in better virologic outcomes. This trial examines further the effect of resistance assay-directed intensification of a PI-containing antiretroviral regimen on viral load. [AS PER AMENDMENT 04/03/01: The antiretroviral regimen need not contain a protease inhibitor.]

Patients are stratified by baseline plasma HIV-1 RNA levels (5,000 copies/ml or less versus greater than 5,000 copies/ml). Patients undergo phenotypic drug resistance testing prior to study entry. Based on the phenotypic results, patients are [AS PER AMENDMENT 11/9/00: selectively] randomized equally to 1 of 3 [AS PER AMENDMENT 11/9/00: 1 of 2] intensification strategies while remaining on their current, initial [AS PER AMENDMENT 11/9/00: (background)] antiretroviral therapy (ART). [AS PER AMENDMENT 04/03/01: ART need not be initial.] A patient is excluded from randomization to an arm if that arm contains a drug to which the patient has phenotypic resistance. Arm A adds abacavir (ABC). Arm B adds amprenavir (APV) [AS PER AMENDMENT 11/9/00: and ritonavir (RTV)]. Arm C adds didanosine (ddI) plus hydroxyurea (HU). [AS PER AMENDMENT 11/9/00: Arm C has been discontinued.] A patient's HIV must be sensitive to at least 3 drugs. [AS PER AMENDMENT 11/9/00: Each patient must be taking at least 3 drugs to which his/her HIV isolate is sensitive, including ABC or APV and at least 2 other drugs that are part of the current, initial (background) ART. If phenotypic resistance testing at screening indicates resistance to a nucleoside reverse transcriptase inhibitor (NRTI) drug in the patient's current, initial (background) ART, then the local investigator may choose to discontinue that drug. However, the patient and local investigator may choose to continue the drug but it will not be considered an active drug per this protocol.] [AS PER AMENDMENT 04/03/01: ART need not be initial.] Patients have regular clinic visits for physical exams and blood tests, including CD4 and CD8 cell counts, plasma HIV-1 RNA assays, and tests for pharmacokinetic variability. In the event of viral rebound of 500 copies/ml or more at Week 12 or later, phenotypic/genotypic drug resistance is assayed. In addition, phenotypic drug resistance is assayed at the primary endpoint (Week 24) and at the end of treatment (Week 48) on all patients.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.
• Are taking 3 or more anti-HIV drugs for at least 24 weeks. (This study has been changed. Previously, only patients taking their first round of anti-HIV drugs, which included a PI, were being studied.)
• Had a viral load below 500 copies/ml while on their anti-HIV drugs, and then had an increase in viral load to between 500 and 10,000 copies/ml. (This study has been changed. Previously, only patients whose levels increased on their first round of anti-HIV drugs were being studied.)
• Have a CD4 cell count of 100 cells/mm3 or more.
• Are age 13 or older (consent of a parent or legal guardian is required if under 18).
• Agree to use 2 methods of birth control during the study and for 60 days after. (This study has changed the birth control requirements.)

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are currently being treated for a serious infection or other serious medical illness.
• Have had certain illnesses in the past.
• Have a fever within 7 days of study entry.
• Have already taken all of the study drugs for more than 4 weeks.
• Are unable to take any of the study drugs.
• Have certain types of cancer.
• Received certain vaccines within 21 days of study entry.
• Have received certain medications.
• Are pregnant or breast-feeding.
• Patients will not be eligible for Group A if they:
• Have a history of hypersensitivity reaction to abacavir.