The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients

A Prospective, Randomized, Comparative Study of the Safety and Efficacy of Clarithromycin Versus Rifabutin Versus the Combination of Clarithromycin Plus Rifabutin for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia or Disseminated MAC Disease in HIV-Infected Patients With CD4 Lymphocyte Counts <= 100 Cells/mm3

To compare the efficacy and safety of clarithromycin alone versus rifabutin alone versus the two drugs in combination for the prevention or delay of Mycobacterium avium Complex (MAC) bacteremia or disseminated MAC disease. To compare other parameters such as survival, toxicity, and quality of life among the three treatment arms. To obtain information on the incidence and clinical grade of targeted gynecologic conditions.

Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.

Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.

Patients are randomized to receive clarithromycin alone, rifabutin alone, or the two drugs in combination daily. Patients are evaluated every 4 weeks for the first 8 weeks and every 8 weeks thereafter for the duration of the study. Patients are followed for 24 months. Per amendment, a pharmacokinetic substudy will be conducted.

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis.

Allowed:

• GM-CSF or G-CSF.
• Erythropoietin.
• Therapies (including antiretrovirals) available through expanded access or treatment IND programs.
• Other non-experimental therapies available by prescription.
• Antihistamines other than those specifically excluded.

Patients must have:

• Evidence or diagnosis of HIV infection or a history of an AIDS-defining condition by CDC criteria.
• CD4 count <= 100 cells/mm3 within 90 days prior to study entry.
• Two baseline blood sample cultures negative for MAC within 30 days of study entry.
• No suspected disseminated MAC disease, in the opinion of the clinician.

NOTE:

• Patients with elevated GGT and/or triglycerides are allowed.

NOTE:

• Patients may co-enroll on ACTG 081/981/181, ACTG 175, ACTG 204, ACTG 193, ACTG 241, or other acceptable protocols.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Known or suspected tuberculous infection or other non-tuberculous mycobacterial infection requiring chemotherapy or chemoprophylaxis (with the exception of isoniazid prophylaxis alone).

NOTE:

• Patients may enroll who successfully completed tuberculosis (TB) treatment and have been off anti-TB drugs for more than 6 months with no symptoms of mycobacterial infection.
• Active TB.
• Known hypersensitivity to study drugs.
• Malabsorption as defined by persistent diarrhea with more than 8 stools per day for > 6 weeks.

Concurrent Medication:

Excluded:

• Frequent (more than once per month), repeated, or continuous treatment courses of quinolones, erythromycin, spiramycin, azithromycin, clarithromycin, or clindamycin.
• Concomitant terfenadine or astemizole.

Prior Medication:

Excluded:

• Prophylaxis with azithromycin, clarithromycin, or rifabutin for more than 4 months.