A Phase III Randomized Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of 3TC/ZDV/1592U89 and 3TC/ZDV/IDV in HIV-1 Infected Antiretroviral Therapy-Naive Subjects.

In this international study, 550 patients are randomized (225 per arm) to receive Combivir in combination with 1592U89 or indinavir. If after 16 weeks (and every 8 weeks thereafter until week 48) a patient has HIV-1 RNA >= 400 copies/ml (by PCR on two occasions >= 1 week and < 4 weeks apart), the patient has the option to switch to open-label therapy consisting of indinavir, 1592U89, and Combivir.

Inclusion criteria

Concurrent Medication:

Allowed:

GM-CSF, G-CSF, and erythropoietin.

Concurrent Treatment:

Allowed:

Local treatment for Kaposi's sarcoma.

Patients must have:

• HIV-1 infection documented by a licensed HIV-1 antibody ELISA and confirmed by Western blot detection of HIV-1 antibody or positive HIV-1 blood culture.
• CD4+ cell count >= 100 cells/mm3 within 14 days prior to study drug administration.
• HIV-1 RNA >= 10,000 copies/ml within 14 days prior to study drug administration.
• No active diagnosis of AIDS according to the 1993 Centers for Disease Control (CDC) AIDS surveillance definition (excluding CD4+ cell counts < 200 cells/mm3).
• 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:

• Malabsorption syndrome or other gastrointestinal dysfunction that may interfere with drug absorption.
• Serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction that would compromise the safety of the patient.

Concurrent Medication:

Excluded:

• Cytotoxic chemotherapeutic agents.
• Agents with documented anti-HIV-1 activity in vitro.
• Foscarnet.
• Immunomodulating agents such as systemic corticosteroids, interleukins, thalidomide, or interferons.
• Terfenadine, astemizole, cisapride, triazolam, midazolam, and ergotamine/dihydroergotamine.

Concurrent Treatment:

Excluded:

• Radiation therapy.
• Other investigational treatments. NOTE:
• Treatments available through treatment IND or other expanded access programs are the exception and evaluated individually.

Patients with the following prior conditions are excluded:

History of relevant pancreatitis or hepatitis in the last 6 months.

Prior Medication:

Excluded:

• Cytotoxic chemotherapeutic agents within 30 days of study drug administration.
• Prior antiretroviral therapy.
• HIV vaccine dose within 90 days of study drug administration.
• Immunomodulating agents such as systemic corticosteroids, interleukins, or interferons within 30 days of study entry.

Prior Treatment:

Excluded:

Radiation therapy within 30 days of study drug administration.

Current alcohol or illicit drug use that may interfere with patient compliance.