A Study of Saquinavir and Zalcitabine, Used Alone and Together, in the Treatment of Advanced HIV Infection in Patients Who Stopped Taking or Who Cannot Take Zidovudine

Patients are randomized to one of three treatment regimens: ddC alone, Ro 31-8959 alone, and ddC plus Ro 31-8959. Treatment continues for at least 48 weeks. Patients are stratified by baseline CD4 count. (Per 09/26/94 amendment, a fourth arm, lower dose Ro 31-8959 plus ddC, was discontinued.)

Inclusion criteria

Concurrent Medication:

Allowed:

• G-CSF and erythropoietin.
• Prophylaxis or chronic suppression/maintenance therapy with dapsone, aerosolized pentamidine, isoniazid, rifampin, fluoroquinolones, pyrazinamide, ethambutol, fluconazole, itraconazole, acyclovir, clotrimazole, nystatin, trimethoprim/sulfamethoxazole, pyrimethamine, folic acid, sulfadiazine, clindamycin, and fansidar.

Concurrent Treatment:

Allowed:

• Limited localized radiation therapy to the skin.

Patients must have:

• Documented HIV infection.
• CD4 count 50 - 300 cells/mm3.
• Received prior AZT that has been discontinued at least 28 days prior to study entry.
• No active opportunistic infection requiring immediate treatment.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Signs or symptoms of peripheral neuropathy.
• Malabsorption or inadequate oral intake (defined as unable to eat one or more meals daily because of chronic nausea, emesis, or abdominal/oral-esophageal discomfort.
• Malignancy, visceral Kaposi's sarcoma, or lymphoma requiring systemic chemotherapy and/or radiotherapy within the next 48 weeks.
• Any grade 3 or worse laboratory or clinical abnormality.
• Inability to comply with protocol requirements.

Concurrent Medication:

Excluded:

• Other antiretroviral drugs.
• Experimental drugs.
• Nephrotoxic or hepatotoxic drugs.
• Drugs likely to cause peripheral neuropathy.
• Antineoplastic agents.
• Biologic response modifiers.

Concurrent Treatment:

Excluded:

• Radiation therapy other than limited localized therapy to skin.

Patients with the following prior conditions are excluded:

• History of non-Hodgkin's lymphoma.
• Unexplained fever >= 38.5 C (101.5 F) persisting for 14 days or longer within the 28 days prior to study entry.
• Unexplained, chronic diarrhea (defined as 3 or more loose stools daily) persisting for 14 days or longer within the 28 days prior to study entry.
• History of grade 2 or worse peripheral neuropathy.

Prior Medication:

Excluded:

• Prior HIV proteinase inhibitor.
• Prior antiretroviral therapy other than AZT.
• Acute therapy for opportunistic infection within 14 days prior to study entry.

Prior Treatment:

Excluded:

• More than 3 units of blood in any 21-day period within 3 months prior to study entry.

Required:

• Prior AZT.