A Study of Zidovudine (AZT) Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Patients With Little or No Previous Treatment

A Randomized, Multicenter, Double-Blind, Phase III, Parallel Study of Zidovudine (AZT) Alone Versus AZT Plus Zalcitabine (Dideoxycytidine; ddC) Versus AZT Plus Saquinavir Mesylate (Ro 31-8959 ; HIV Proteinase Inhibitor) Versus AZT Plus ddC Plus Ro 31-8959 in Previously Untreated or Minimally Pretreated HIV-Infected Patients With CD4 Lymphocyte Counts From 50 to <= 350 Cells/mm3

To compare, in zidovudine (AZT)-naive patients, the safety, tolerance, and efficacy of saquinavir mesylate (Ro 31-8959) alone versus AZT alone versus AZT in combination with Ro 31-8959, zalcitabine (ddC), or both. To compare various disease markers among the different regimens.

Patients are randomized to receive a minimum of 80 weeks of AZT alone, AZT plus ddC, AZT plus Ro 31-8959, or all three drugs.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Erythropoietin and G-CSF.

Concurrent Treatment:

Allowed:

• Local skin radiotherapy.

Patients must have:

• HIV infection.
• CD4 count 50 - 350 cells/mm3.
• No prior antiretroviral therapy OR less than 16 weeks of prior AZT.
• No acute serious opportunistic infections requiring immediate treatment.
• No unexplained fever persisting for 14 days within 90 days prior to study entry.
• No significant unexplained diarrhea persisting for 14 days within 30 days prior to study entry.
• No visceral Kaposi's sarcoma or lymphoma currently requiring chemotherapy and/or radiotherapy.
• Life expectancy of at least 80 weeks.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malabsorption.
• Severe chronic diarrhea.
• Inadequate oral intake (unable to eat one or more meals daily because of chronic nausea, emesis, or abdominal/oral-esophageal discomfort).
• Any grade 3 or worse toxicity.
• Inability to comply with study requirements.

Concurrent Medication:

Excluded:

• Other investigational agents.
• Antineoplastic agents.
• Biologic response modifiers (including interferons).
• Foscarnet.
• Anti-HIV drugs other than the study drugs.

Concurrent Treatment:

Excluded:

• Radiotherapy (other than local skin radiotherapy).

Patients with the following prior condition are excluded:

History of non-Hodgkin's lymphoma.

Prior Medication:

Excluded:

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