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To compare the effectiveness and toxicity of didanosine (ddI) and zidovudine (AZT) in patients with AIDS, advanced AIDS-related complex (ARC), or asymptomatic infection with CD4 counts < 200 cells/mm3. AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. AMENDED: 9/28/90 Patients are assigned to one of 2 treatments under a double-blind, randomly allocated, experimental design if their duration of prior AZT therapy is 0 to 16 weeks. (Patients who entered with no more than 16 weeks prior AZT and who were randomized to ddI will continue to be dosed at that level, adjusted for weight, and followed as originally planned.) Patients are assigned to one of 3 treatments as explained prior to this amendment if their duration of prior to AZT therapy is greater than 16 weeks. Original design: Patients are assigned to one of three treatments under a double-blind randomly allocated experimental design. ddI will be administered at two dose levels. It is anticipated that patients will be seen as outpatients every 2 weeks for the first 4 weeks of the study and monthly thereafter. This study continues for at least 18 months after the entry of the first subject.
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.