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To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons with AIDS, including individuals who have or have not received prior MAC prophylaxis. It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones. It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones. Patients are randomized to one of three treatment arms containing clarithromycin in combination with ethambutol, rifabutin, or both. Clarithromycin alone is taken on days 1 through 3 to determine tolerance and rifabutin and/or ethambutol is added on day 3. AS PER AMENDMENT 7/2/97: Patients may elect to add ritonavir or indinavir to their treatment regimen. Treatment continues daily for 48 weeks. In the absence of a dose-limiting toxicity, those patients who are determined to be complete or partial responders continue on the regimen to which they were originally assigned. Patients who have failed or relapsed on originally assigned MAC therapy, must have their therapy amended to receive clarithromycin and at least two other drugs not included in their originally assigned regimen. Patients are followed twice in the first week, then every 2 weeks for the first 2 months, then monthly for the next 4 months, and then every 2 months thereafter until the end of 12 months. PER AMENDMENT 10/10/96: NOTE: Any patient who develops a toxicity to rifabutin or ethambutol after week 12 or thereafter will be offered the option of being registered to a salvage regimen of 2 new drugs not previously received, plus clarithromycin to continue for the study duration.
Inclusion Criteria Concurrent Medication: Allowed: * Antiretroviral therapy. * Maintenance or prophylactic therapy for other opportunistic infections (with the exception of specifically excluded drugs). * Carbamazepine or theophylline. * Isoniazid for TB prophylaxis. PER AMENDMENT 10/10/96: * Therapy for acute infectious processes, other than MAC, provided that the patient is stable on the therapy. * Fluconazole therapy for maintenance or suppression of fungal infections, providing the patient has been on a stable dose for at least 4 weeks. PER AMENDMENT 7/02/97: * If a patient elects to receive indinavir, ORTHO/NOVUM 1/35 is an acceptable means of birth control. Patients must have: * HIV infection. * Disseminated MAC disease. * Life expectancy of at least 8 weeks. * Consent of parent or guardian if under 18 years of age. NOTE: * This protocol is approved for prisoner participation. Prior Medication: Allowed: PER AMENDMENT 10/10/96: * Therapy for acute infectious processes, other than MAC, prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Active mycobacterial infection other than MAC that requires treatment, with the exception of isoniazid used solely for TB prophylaxis. Concurrent Medication: Excluded: * Other antimycobacterial drugs (with the exception of isoniazid for TB prophylaxis). * Other investigational drugs unless approved by protocol chair. PER AMENDMENT 7/2/97: * For patients who elect to receive indinavir or ritonavir: * Terfenadine, astemizole, cisapride, triazolam, or midazolam. * For patients who elect to receive ritonavir: * alprazolam, amiodarone, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, dihydroergotamine, ergotamine, estazolam, encainide, flecainide, flurazepam, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine or zolpidem. * For patients who elect to receive indinavir: * oral contraceptives other than ORTHO/NOVUM as a sole form of birth control. * For patients randomized to a rifabutin-containing arm: * oral contraceptives or Norplant as a sole form of birth control. Patients with the following prior condition are excluded: * History of severe hypersensitivity to erythromycin, clarithromycin, azithromycin, ethambutol, rifampin, or rifabutin (including Type 1 hypersensitivity reaction, Stevens-Johnson syndrome, hepatitis, optic neuritis, or exfoliative dermatitis). Prior Medication: Excluded: * Empiric or presumptive antimycobacterial therapy prior to study entry if \> 14 days, within 90 days prior to entry. NOTE: * Patients unwilling to discontinue presumptive therapy or empiric therapy may be enrolled with the permission of the protocol chairs, however, if they are without a MAC positive blood culture at baseline, they will have study medications discontinued (AS PER AMENDMENT 7/2/97). PER AMENDMENT 10/10/96: * Treatment with clarithromycin or ethambutol within 4 days of initiation of study medications. * Treatment with rifabutin or rifampin within 7 days of initiation of study medications.