Inclusion Criteria

Concurrent Medication:

Required:

• Aerosolized pentamidine (300 mg every 4 weeks).

Allowed:

• Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus infection.
• Ganciclovir for patients developing cytomegalovirus (CMV) infection while in study.
• Erythropoietin for patients under the relevant treatment IND.
• Treatment of opportunistic infections with other than sulfonamide-containing regimens.
• Aspirin, acetaminophen, or non-steroidal anti-inflammatory agents is discouraged, but is permitted for as short a period of time as possible.
• Chronic use of trimethoprim - sulfamethoxazole or other sulfonamide preparations is not encouraged while on study.

Patients must:

• Have had the diagnosis of AIDS or advanced AIDS related complex (ARC).
• Have received AZT therapy for at least 12 months, with a minimal daily dose of 500 mg/day and with no more than 60 days off AZT therapy within the 12 month period; medical records with documentation of AZT dosing must be provided.
• Provide informed consent (guardian as appropriate).
• Be available for follow-up for at least 6 months.
• Have the inclusion laboratory values within approximately 14 days of initiating therapy (except for CD4 cell counts).
• Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell counts < 300 cells/mm3.

Allowed:

• Positive blood culture for Mycobacterium avium or Cytomegalovirus.
• Prior history of toxoplasmosis, Herpes simplex, Cryptococcus, or Pneumocystis carinii pneumonia (PCP) requiring chronic suppressive therapy.
• Occasional premature atrial or ventricular contractions.

Prior Medication:

Required:

• Zidovudine (AZT) therapy for at least 12 months, with a minimal daily dose of 500 mg/day, and with no more than 60 days off AZT therapy within the 12-month period (documentation of AZT dosing must be provided).

Allowed:

• Intralesional agents.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
• AIDS-dementia complex = or > stage 2.
• Active AIDS defining opportunistic infections not specifically allowed.
• Intractable diarrhea.
• Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyperreflexia.
• Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
• History of seizures within past 2 years or currently requiring anticonvulsants for control.
• History of past or current heart disease.
• Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
• Life expectancy < 3 months.

Concurrent Medication:

Excluded:

• Isoniazid (INH). Neurotoxic drugs. Oral acidifying agents.

Patients with the following are excluded:

• Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
• AIDS-dementia complex = or > stage 2.
• Active AIDS defining opportunistic infections not specifically allowed.
• Intractable diarrhea.
• Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
• History of seizures within past 2 years or currently requiring anticonvulsants for control.
• History of past or current heart disease.
• Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
• Life expectancy = or < 3 months.
• Previous participation in any study of ddI, ddC or d4T.

Prior Medication:

Excluded:

• Ganciclovir (DHPG).
• Excluded within 1 month of study entry:
• ddI and any other antiretroviral drug or investigational anti-HIV agent except for zidovudine (AZT).

Interferons.

• Immunomodulating drugs.
• Cytotoxic agents not specifically allowed.
• Neurotoxic drugs.

Excluded within 3 months of study entry:

• Ribavirin.

Prior Treatment:

Excluded within 14 days of study randomization:

• Blood transfusion.

Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.