To compare the efficacy, safety and tolerance, and other clinical and immunologic effects of zidovudine (AZT) plus zalcitabine (dideoxycytidine; ddC), AZT plus didanosine (ddI), and AZT alternating monthly with ddI as measured by differences in survival among HIV-infected persons who have received 6 or more months of nucleoside monotherapy and have a CD4 count greater than or equal to 50 cells/mm3.

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

Patients are randomized to one of three treatment arms: AZT plus ddI, AZT plus ddC, and AZT alone alternating monthly with ddI. Half of the patients receiving AZT alternating monthly with ddI will start with AZT, while the other half will start with ddI. Treatment continues until death or termination of the study. Patients are followed every 4 weeks. The study will include a subset of patients for whom virologic, pharmacokinetic, and macroneurologic assessments will be made.

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis.

Allowed:

• Erythropoietin.
• Prophylaxis for MAI or fungal infections.
• Antibiotics.
• Over-the-counter, alternative, or regularly prescribed drugs.
• Steroids, if for < 21 days.

Concurrent Treatment:

Allowed:

• Radiation therapy for cutaneous Kaposi's sarcoma.

Patients must have:

• HIV infection.
• CD4 count <= 50 cells/mm3.
• Prior nucleoside monotherapy for at least 6 months.
• Life expectancy of at least 6 months.

Prior Medication: Required:

• Nucleoside monotherapy for at least 6 months. Active alcohol or drug abuse.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Severe peripheral neuropathy.
• Psychological or emotional problems sufficient to prevent study compliance.

Concurrent Medication:

Excluded:

• Systemic chemotherapy for malignancy.
• Acute or induction therapy for opportunistic infection.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.
• Grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.

Prior Medication:

Excluded:

• Non-study nucleosides or biologic response modifiers within 7 days prior to study entry.
• Acute therapy for opportunistic process within 14 days prior to study entry.
• Acute systemic therapy for other medical conditions within 14 days prior to study entry.