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.

Condition	Treatment or Intervention	Phase
Mycoses Mycobacterium avium-intracellulare Infection HIV Infections	Drug: Azithromycin  Drug: Rifabutin  Drug: Fluconazole	Phase III

Further Study Details: 

Expected Total Enrollment:  720

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.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

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.

California
      UCSD Treatment Ctr / Dept of Medicine and Pediatrics, San Diego,  California,  92103,  United States
      Santa Clara Valley Med Ctr, San Jose,  California,  951282699,  United States
      Harbor - UCLA Med Ctr, Torrance,  California,  90509,  United States
      UCI Med Ctr, Orange,  California,  92668,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Massachusetts
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
Pennsylvania
      Univ of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77005,  United States
      Univ of Texas Southwestern Med Ctr, Dallas,  Texas,  75235,  United States
      Houston Veterans Administration Med Ctr, Houston,  Texas,  77030,  United States

Study ID Numbers:  226A; 066-174
Record last reviewed:  April 1996
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002122
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08