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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Mycoses, Mycobacterium Avium-Intracellulare Infection, HIV Infections

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Rifabutin
* Drug: Fluconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Azithromycin|nan|
|Drug: Rifabutin|nan|
|Drug: Fluconazole|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mycoses, Rifabutin, Mycobacterium avium-intracellulare Infection, Drug Therapy, Combination, Fluconazole, Acquired Immunodeficiency Syndrome, Azithromycin