A Randomized Study of Daily and Intermittent Prophylactic Regimens for the Prevention of Disseminated Mycobacterium Avium Complex (MAC) and Fungal Infections in HIV-Infected Patients

Pfizer

Status and phase: Completed; Phase 3

Conditions: Mycobacterium Avium-Intracellulare Infection; Mycoses; HIV Infections

Treatments: Drug: Fluconazole; Drug: Azithromycin; Drug: Rifabutin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002122

226A

066-174

Details and patient eligibility

About

PRIMARY: To determine the efficacy of azithromycin and rifabutin alone and in combination for the prevention of disseminated Mycobacterium avium Complex (MAC) infection in HIV-infected patients. To determine the efficacy of daily versus weekly fluconazole for the prevention of deep fungal infections in this patient population.

SECONDARY: To determine the incidence of bacterial (including mycobacterial) infections, cryptosporidiosis, and toxoplasmosis in azithromycin versus non-azithromycin containing regimens. To determine the incidence of oropharyngeal and vaginal candidiasis in patients treated with daily versus weekly fluconazole. To compare survival and outcomes of primary endpoints in the treatment arms.

Full description

Patients are randomized to receive azithromycin alone, rifabutin alone, or the two drugs in combination for MAC prophylaxis. Patients in each treatment group further receive one of two doses of concomitant fluconazole for deep fungal prophylaxis, unless specifically excluded for fluconazole randomization. Patients are followed for 1 to 2 years.

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Preventive therapy with isoniazid for M. tuberculosis.
• Maintenance therapy for CMV retinitis.

Patients must have:

• HIV infection or history of an AIDS-defining condition by CDC criteria.
• One documented CD4 count < 100 cells/mm3 within 12 months prior to study entry.
• NO active MAC disease, MAC bacteremia, or active mycobacterial infection (tuberculous or nontuberculous).
• NO acute opportunistic infection.
• Life expectancy of more than 6 months.
• Consent of parent or guardian if less than legal age of consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

ALL PATIENTS -

• Unexplained fevers, elevation in alkaline phosphatase, pancytopenia, abnormal liver function tests, or odynophagia for which the diagnoses of MAC and fungal infections have not been excluded.
• Serious hypersensitivity reactions to macrolides or rifampin.
• Unable to tolerate oral medications. FOR FLUCONAZOLE RANDOMIZATION -
• Serious hypersensitivity reaction to fluconazole.
• Active fungal infection (cryptococcosis, histoplasmosis, blastomycosis, aspergillosis, Candida esophagitis, thrush, vaginal candidiasis).
• Positive baseline urine cryptococcal culture.

Concurrent Medication:

Excluded for fluconazole randomization:

• Maintenance therapy for deep fungal infections.
• Chronic therapy with ketoconazole or fluconazole.