Comparison of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (ddC) Versus Ro 31-8959 Plus AZT Plus ddC

Double-Blind, Randomized, Phase II Study of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (Dideoxycytidine; ddC) Versus Ro 31-8959 Plus AZT Plus ddC

PRIMARY: To determine the efficacy and toxicity of three treatment regimens: saquinavir mesylate (Ro 31-8959) plus zidovudine (AZT) vs. AZT plus zalcitabine (dideoxycytidine; ddC) vs. Ro 31-8959 plus AZT plus ddC.

SECONDARY: To investigate the pharmacokinetics and effects on various clinical parameters of the three regimens.

Inclusion Criteria

Prior Medication: Required:

• At least 4 months total of AZT at some point in the past, alone or in combination with other antiretroviral therapy.

Patients must have:

• HIV seropositivity.
• Diagnosis of AIDS, ARC, PGL, or asymptomatic infection.
• CD4 count > 50 to <= 300 cells/mm3.
• Life expectancy of at least 6 months.
• Prior AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Acute serious opportunistic infections requiring immediate treatment, including (but not limited to) tuberculosis, CMV, cryptococcal meningitis, disseminated MAC, cerebral toxoplasmosis, and Pneumocystis carinii pneumonia.
• Known intolerance to Ro 31-8959, AZT, or ddC.
• Symptoms suggestive of pancreatitis.
• Moderate or severe peripheral neuropathy as evidenced by discomfort from numbness, tingling, burning or pain of the extremities or any related symptoms that are accompanied by an objective finding.
• Visceral Kaposi's sarcoma.
• Lymphoma that will require therapy within the next 6 months.
• Transfusion dependence.

Concurrent Medication:

Excluded:

• Investigational or antineoplastic agents.

Concurrent Treatment:

Excluded:

• Radiotherapy (other than local skin radiotherapy).
• Transfusions.

Prior Medication:

Excluded:

• Any antiretroviral agent (other than AZT) or immunomodulatory therapy within 14 days prior to study entry.
• Prior treatment with an HIV proteinase inhibitor.