Tolerance, Safety, and Activity of Rifapentine Alone and in Combination Therapy in AIDS Patients With Mycobacterium Avium Complex Bacteremia.

This open-label, sequential study is conducted in two parts: a monotherapy phase and a combination treatment phase.

In the monotherapy phase sequential 3-patient cohorts receive 1 of 3 doses of rifapentine monotherapy.

In the combination treatment phase, 12 patients each are randomized to one of three arms:

Arm I: Rifapentine (assigned dose level based on monotherapy phase) plus azithromycin.

Arm II: Rifapentine (assigned dose level) plus clarithromycin. Arm III: Rifapentine (assigned dose level) plus ethambutol.

Inclusion criteria

Patients must have:

• Documented positive HIV serology status.
• Documented AIDS.
• Positive blood culture for MAC from the study-designated microbiology laboratory. NOTE:
• Patients with presumed MAC bacteremia, as evidenced by positive blood, bone marrow, or liver biopsy culture analyzed locally, may be enrolled pending confirmation.
• Minimum of two MAC-associated symptoms, defined as >= grade 1 fever; > grade 1 night sweats, fatigue, diarrhea, abdominal pain, or anorexia; or weight loss > 5% reported within 4 weeks prior to study entry.
• Life expectancy of at least 3 months.

Prior Medication:

Allowed:

MAC prophylaxis with medications other than study drugs (5-day washout period required).

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Pulmonary tuberculosis.
• Infections requiring the use of disallowed medications.
• Serious diseases that introduce undue risks for adverse reactions to study medication.

Concurrent Medication:

Excluded:

• Terfenadine.
• Treatment for pulmonary TB.
• Study drugs from an outside source.
• Medications with anti-MAC activity (i.e., amikacin, ciprofloxacin, clofazimine, rifampin, and rifabutin).

Patients with the following prior conditions are excluded:

• History of hypersensitivity to rifabutin, rifampin, clarithromycin, erythromycin, azithromycin, or ethambutol.
• Previous episode of uveitis.

Prior Medication:

Excluded:

• Prophylactic treatment for MAC with rifabutin or any of the study medications.
• Azithromycin within the 3 weeks prior to randomization.
• Any investigational drug during the 4 weeks prior to randomization.