Pilot Study to Determine the Feasibility of Itraconazole for Suppression of Relapse of Disseminated Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome

Inclusion Criteria

Concurrent Medication:

Itraconazole therapy must begin no more than 6 weeks after discontinuing primary amphotericin B therapy; itraconazole therapy may begin immediately after stopping the primary therapy with amphotericin B.

Allowed:

• Oral contraceptives.
• Methadone.
• Narcotics.
• Acyclovir.
• Acetaminophen.
• Sulfonamides.
• Trimethoprim / sulfamethoxazole.
• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis (patients with a total CD4+ count < 200 or a history of PCP should receive PCP prophylaxis).
• Treatment IND drugs.
• Zidovudine.
• Topical antifungals.
• Discouraged:
• Antacids.
• Sucralfate.
• H2 blockers.

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Prior Medication:

Required:

• Prior treatment with amphotericin B for disseminated histoplasmosis:
• minimum total dose of 15 mg/kg for patients < 67 kg, or 1 g for patients > 67 kg; must have been administered over 6 months or less.

Allowed:

• Amphotericin B as maintenance therapy for a maximum of 6 weeks following completion of primary therapy.
• Zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• History of allergy to, or intolerance of, imidazoles or azoles.
• Clinical findings of active histoplasmosis.
• Histoplasmosis of the central nervous system.
• Inability to take oral medications reliably or severe malabsorption syndrome.
• Malignancies requiring cytotoxic therapy.
• Culture-proven systemic Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, coccidioidomycosis, or cryptococcosis.

Concurrent Medication:

Excluded:

• Amphotericin B as maintenance therapy.
• Immunostimulants.
• Ketoconazole.
• Systemic antifungals.
• Steroids in excess of physiologic replacement doses.
• Cytotoxic chemotherapy.
• Investigational agents not specifically allowed.
• Antacids for 4 hours before and 4 hours after itraconazole.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following conditions are excluded:

• History of allergy to, or intolerance of, imidazoles or azoles.
• Clinical findings of active histoplasmosis.
• Histoplasmosis of the central nervous system.
• Inability to take oral medications reliably or severe malabsorption syndrome.
• Malignancies requiring cytotoxic therapy.
• Culture-proven systemic Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, coccidioidomycosis, or cryptococcosis.

Prior Medication:

Excluded within 30 days of study entry:

• Immunostimulants.
• Ketoconazole.
• Systemic antifungals.
• Steroids in excess of physiologic replacement doses.
• Cytotoxic chemotherapy.

Prior Treatment:

Excluded:

• Lymphocyte replacement.

Risk Behavior:

Excluded:

• Patients who in the opinion of the investigator would be undependable with regard to adherence to protocol.

Inclusion criteria are:

• HIV infection documented by presence of antibody, by ELISA with Western blot confirmation, or serum p24 antigen, or by recovery of HIV in culture.
• Acute first episode of disseminated histoplasmosis documented by recovery and identification of H. capsulatum from cultures obtained from extrapulmonary sites.
• Oriented to person, place, and time, and able to give written informed consent.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety