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To evaluate and compare the effectiveness and toxicity associated with didanosine ( ddI ) and zalcitabine ( dideoxycytidine; ddC ) in patients with HIV infection who are intolerant of or have failed zidovudine ( AZT ) therapy. Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT. Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT. After baseline screening, patients are randomized to one of two treatment arms (ddI or ddC). Subjects are evaluated biweekly for the first 4 weeks of study, at 2 months, and every other month thereafter. Three dose levels of ddI (based on patient's weight at study entry) are compared with two dose levels of ddC (also based on patient weight). Patients who reach a new progression-of-disease primary endpoint after at least 12 weeks of treatment or a drug intolerance endpoint have the option of switching over to the alternate study drug; however, participants are encouraged to remain on their original drug assignment whenever possible. For any switchover, patients must be off the originally assigned drug for at least 72 hours before switching. Only one switchover is allowed.
Inclusion Criteria Concurrent Medication: Allowed: * Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent). * Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy. * Interferons for maintenance therapy of Kaposi's sarcoma. * GM-CSF. Required: * Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is \< 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician. * NOTE: There is potential interaction of ddI and dapsone. Concurrent Treatment: Allowed: * Transfusion, erythropoietin. Patients must have the following: * Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months. * AZT intolerance - rechallenge is not required for patients exhibiting = or \> grade III cutaneous symptoms. * Diagnosis of AIDS or CD4+ = or \< 300 cells/mm3 OR AIDS-defining illness other than Kaposi's sarcoma. * Willingness and ability to comply with protocol. * Informed consent must be obtained for all study participants in accordance with state law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: * Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis. * Active opportunistic infection. Concurrent Medication: Excluded: * Other antiretroviral agents. * Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided. Concurrent Treatment: Excluded: * Other concurrent antiretroviral clinical trials. Patients with the following are excluded: * History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC. * Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease. * Receiving acute therapy for active AIDS defining opportunistic infection on enrollment. Prior Medication: Excluded: * Didanosine (ddI). * Dideoxycytidine (ddC) . Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.