The Safety and Effectiveness of Zidovudine Plus Lamivudine, Used With and Without 1592U89, in HIV-1 Infected Children Who Have Taken Anti-HIV-1 Drugs

Patients are randomized to receive blinded treatment with ZDV/3TC alone or in combination with 1592U89, orally for 16 weeks. If after the 16-week period certain criteria are met, patients may have the option to switch to open-label treatment for the remainder of the study period.

Inclusion criteria

Concurrent Medication:

Allowed:

• Intravenous immunoglobulin G, erythropoietin, G-CSF and GM-CSF.
• Opportunistic infection prophylaxis.

Patients must have:

• HIV-1 infection documented by:

< 18 months of age:

• one positive viral test culture and one other positive viral test (culture, PCR, p24 antigen, or Immune Complex Dissociation p24 antigen) on two different specimens.

>= 18 months of age:

• two positive viral tests as stated above, one or both of which may be determined by a federally documented ELISA and confirmed by Western blot or Indirect Fluorescent Antibody test.
• Any of the CDC Categories:
• 1, 2, 3, and N, A, B, and C of the 1994 Revised Classification System for HIV Infection in Children Less than 13 Years of Age.
• CD4+ count >= 15% within 14 days prior to study drug administration.
• No active or ongoing AIDS-defining opportunistic infection that precludes absorption of study drug or observation of a study parameter.
• Signed, informed consent from parent or legal guardian for patients under 18 years of age.

Exclusion criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Serious bacterial infection that precludes absorption of study drug or observation of a study parameter.
• Documented hypersensitivity to a nucleoside analog.
• Co-enrollment in certain opportunistic infection protocols is not exclusionary if approval is obtained.
• Malignancy.
• Life-threatening infection or other chronic disease that may compromise patient safety.
• Grade 3/4 clinical or laboratory toxicity or current grade 2 or higher pancreatic amylase or lipase toxicity as defined by the ACTG Toxicity Tables within 14 days prior to study entry.

Concurrent Medication:

Excluded:

• Other anti-HIV therapy.
• Probenecid.
• Biologic response modifier (unless listed under included concurrent medication) and megestrol acetate.
• Human growth hormone.
• Immunomodulators and cytotoxic chemotherapeutic agents.
• Systemic corticosteroids > 14 days without approval.
• Investigational agents.

Concurrent Treatment:

Excluded:

Radiation therapy.

Patients with the following prior conditions are excluded:

• History of clinically relevant pancreatitis or hepatitis within the past 6 months.
• Participation in a vaccine trial.

Prior Medication:

Excluded:

• Protease inhibitor therapy within 2 weeks prior to randomization.
• Interleukins or interferons within 30 days prior to study drug administration.
• Investigational drugs within 14 days prior to randomization.
• HIV vaccine dose within past 30 days.

Required:

> 12 weeks prior antiretroviral therapy and unchanged therapy 12 weeks prior to screening.