Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs

Inclusion Criteria

Concurrent Medication:

Allowed:

• IVIG and opportunistic infection prophylaxis will be allowed.
• Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF) will be allowed for the management of hematologic toxicity.
• Treatment with trimethoprim is allowed at the discretion of the principal investigator.

Patients must have:

• Laboratory evidence (at least 2 viral tests) of HIV-1 infection.
• Clinical and immunological stability [maintained CDC category 1 or 2 immunologic status for past 4 months and no new CDC category (diagnosis within the past year)].
• Patients must have received continuous antiretroviral therapy for the past 16 weeks (missing no more than 6 weeks of therapy during the previous 16 weeks).

AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2:

• Viral load >= 10,000 and < 100,000 copies/ml at week 12, 24, or 36 in children initially assigned to Arm I (ZDV + 3TC) of PRAM-1 and currently on study.

Prior Medication:

Required:

• Patients must have received continuous antiretroviral therapy for the past 16 weeks.

Allowed:

• Patients who have received immunomodulator therapy as part of perinatal clinical trials or in trials for HIV- exposed infants are eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Current grade 3/4 clinical or laboratory toxicity and/or current grade 2 or higher amylase/lipase toxicity.
• Active opportunistic infection and/or serious bacterial infection.
• Current diagnosis of malignancy.

Concurrent Medication:

Excluded:

• Current antiretroviral therapy identical to any of the following regimens:
• ZDV + 3TC, d4T + ritonavir and ZDV + 3TC + ritonavir.
• Concurrent therapy with any other anti-HIV-1 therapy, biologic response modifiers (EPO, G-CSF and GM-CSF allowed), human growth hormone and megestrol acetate.
• Use of continuous systemic corticosteroids (>= 14 days duration) is not allowed.
• Medications that are incompatible with ritonavir.
• Probenecid and daily intravenous pentamidine.

[AS PER AMENDMENT 10/23/98: The following are excluded in patients receiving indinavir:

• terfenadine, astemizole, cisapride, rifampin, rifabutin, triazolam, ketoconazole, clarithromycin, carbamazepine, phenobarbital, phenytoin, calcium channel blockers, midazolam, and ergot derivatives.]

Patients with the following prior conditions and symptoms are excluded:

• Documented hypersensitivity to a therapy included in any of the treatment arms.

Prior Medication:

Excluded:

Investigational drug therapy within 2 weeks prior to randomization.

NOTE:

• Co-enrollment in ACTG 219, ACTG 220 and certain ACTG opportunistic infection protocols is allowed.