The Safety and Effectiveness of 935U83 in HIV-Infected Patients

Patients (10 per dose level) are randomized to receive 1 of 4 doses of 935U83 every 8 hours for 12 weeks. Five patients at each dose level must complete 4 weeks of treatment without serious toxicity before subsequent patients are entered at the next higher dose. If lack of antiretroviral effect or unacceptable toxicity is demonstrated at a particular dose level, the dose regimens may be adjusted.

Inclusion criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis for patients whose CD4 counts fall below 200 cells/mm3 or who develop PCP during study participation.

Allowed:

• Acute treatment and secondary prophylaxis for tuberculosis, Mycobacterium avium intracellulare, toxoplasmosis, histoplasmosis, cryptococcosis, disseminated candidiasis, or cytomegalovirus infection.

Patients must have:

• HIV infection.
• CD4 count 200 - 500 cells/mm3.
• No history of or current AIDS-defining indicator disease by CDC criteria.
• No antiretroviral therapy within the past 6 months.
• Consent of parent or guardian if less than 18 years of age.

Exclusion criteria

Co-existing Condition:

Patient with the following symptoms or conditions are excluded:

• Current evidence of chronic hepatitis of any etiology.
• Seropositivity for HBsAg or hepatitis C virus by second generation ELISA.

Concurrent Medication:

Excluded:

• Cytotoxic chemotherapy.
• Other antiretroviral drugs.
• Immunomodulators.
• Foscarnet.
• GM-CSF or G-CSF.
• Erythropoietin.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following prior conditions are excluded:

History of chemical, viral, or alcohol-induced clinical hepatitis within the past 3 years.

Prior Medication:

Excluded within the past 6 months:

• Any antiretroviral therapy.
• HIV immunotherapeutic vaccine.

Excluded within the past 4 weeks:

• Cytotoxic chemotherapy.
• Immunomodulating agents such as systemic corticosteroids, IL-2, alpha interferon, beta interferon, or gamma interferon.

Prior Treatment:

Excluded within the past 4 weeks:

• Radiation therapy. Current alcohol or illicit drug use that may interfere with study compliance.