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.

• Drug: Saquinavir
• Drug: Zidovudine
• Drug: Zalcitabine

• Schapiro JM, Lawrence J, Speck R, Winters MA, Efron B, Coombs RW, Collier AC, Merigan TC. Resistance mutations to zidovudine and saquinavir in patients receiving zidovudine plus saquinavir or zidovudine and zalcitabine plus saquinavir in AIDS clinical trials group 229. J Infect Dis. 1999 Jan;179(1):249-53.
• Collier AC, Coombs RW, Schoenfeld DA, Bassett R, Baruch A, Corey L. Combination therapy with zidovudine, didanosine and saquinavir. Antiviral Res. 1996 Jan;29(1):99.
• Noble S, Faulds D. Saquinavir. A review of its pharmacology and clinical potential in the management of HIV infection. Drugs. 1996 Jul;52(1):93-112. Review.
• Vanhove GF, Gries JM, Verotta D, Sheiner LB, Coombs R, Collier AC, Blaschke TF. Exposure-response relationships for saquinavir, zidovudine, and zalcitabine in combination therapy. Antimicrob Agents Chemother. 1997 Nov;41(11):2433-8.
• Collier AC, Coombs RW, Schoenfeld DA, Bassett RL, Timpone J, Baruch A, Jones M, Facey K, Whitacre C, McAuliffe VJ, Friedman HM, Merigan TC, Reichman RC, Hooper C, Corey L. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N Engl J Med. 1996 Apr 18;334(16):1011-7.
• Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, Allan JD, Goldsmith JC, Powderly WG. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med. 1995 Jan 1;122(1):24-32.

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.