A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS

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.