Inclusion Criteria

Concurrent Medication:

Required:

• Aerosolized pentamidine (300 mg every 4 weeks using a Respirgard II nebulizer). In the event of physiological intolerance, alternative prophylaxis may be: Trimethoprim / sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg/day.

Allowed:

Maintenance therapy for active AIDS defining opportunistic infections for patients with 9 to 47 weeks' experience with zidovudine (AZT).

Treatment of opportunistic infections with other than sulfonamide containing drugs:

• Pyrimethamine and sulfadiazine or clindamycin for suppression of toxoplasmosis acquired after study entry; fluconazole or amphotericin B for suppression of cryptococcosis or ketoconazole for candidiasis.

Intravenous acyclovir for up to 10 days. Erythropoietin for patients under the relevant treatment IND. Analgesics, antihistamines, antiemetics, antidiarrheal agents for symptomatic therapy for toxicities.

Isoniazid (INH) if no other acceptable therapy is available.

Metronidazole may be used for single courses of therapy not to exceed 14 days within consecutive 90 day intervals. Note:

• Ketoconazole and dapsone should be taken 2 hours before or 2 hours after taking ddI (amendment 5/20/91).

Concurrent Treatment:

Allowed:

• Blood transfusions for hemoglobin toxicity.

Patients must:

• Have a diagnosis of AIDS or advanced AIDS related complex (ARC), or per 8/09/90 amendment, asymptomatic HIV infection with CD4 count = or < 200 cells/mm3.
• Be either naive to zidovudine (AZT) or have taken AZT for = or < 48 weeks.
• Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry. For patients with 2 months or less experience with AZT, PCP infection will be the single and only AIDS-defining infection and must have been within 120 days of study entry. Per amendment, other AIDS-defining conditions are allowed in the 8 weeks prior to study entry (for patients in the AZT stratum).Only one episode of PCP is permitted unless patient has > 2 months AZT experience in which case > 1 prior episode of PCP infection is allowed.
• Not have experienced a major intolerance to AZT at doses of at least 500 mg if the patient was on AZT therapy for = or < 48 weeks. A major intolerance is defined as recurrent grade 3 or greater toxicity which results in discontinuation of drug.

Allowed:

• Basal cell carcinoma.
• In situ carcinoma of the cervix.
• Occasional premature atrial or ventricular contraction.
• Patients developing new opportunistic infections after study entry will remain on this protocol.
• Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell counts < 300 cells/mm3.

Prior Medication:

Allowed:

• Previous treatment with zidovudine (AZT) up to 48 weeks.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or diseases are excluded:

• Kaposi's sarcoma (KS) with evidence of visceral disease or where KS requires chemotherapy; subjects with localized KS having CD4 counts = or > 200 cells/mm3.
• AIDS-dementia complex = or > stage 2.
• Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
• Intractable diarrhea.
• History of seizures within past 6 months or currently requiring anticonvulsants for control.
• History of past or current heart disease.
• Presence of a malignancy likely in the investigators opinion to require cytotoxic myelosuppressive chemotherapy during the expected course of this trial.

Concurrent Medication:

Excluded:

• Oral acidifying agents.
• Neurotoxic drugs. NOTE: If patients require therapy for PCP with IV pentamidine, study mediation is stopped.

Patients with the following are excluded:

• Active AIDS defining events. Maintenance therapy for prior AIDS-defining opportunistic infections is permitted.
• Intolerance to AZT at doses of 500 mg because of recurrent grade 3 toxicity or greater which resulted in discontinuation of drug.
• Neoplasms not specifically allowed.
• Previous enrollment in any study of ddI, ddC or d4T.
• > 48 weeks of AZT therapy.
• An opportunistic infection not adequately controlled with suppressive therapies allowed in the protocol.
• Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance study therapy.
• Life expectancy = or < 6 months.

Prior Medication:

Excluded:

• Ganciclovir.
• AZT for = or > 48 weeks.

Excluded within 14 days of study entry:

• Erythropoietin (Eprex).

Excluded within 30 days of study entry:

• Anti-HIV therapy other than AZT.
• Biologic response modifiers.
• Other investigational drugs.
• Corticosteroids.
• Neurotoxic drugs.

Excluded within 90 days of study entry:

• Ribavirin.

Prior Treatment:

Excluded within 14 days of study entry:

• Transfusion.

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