Pilot Study To Determine the Feasibility of Itraconazole for Primary Treatment and Suppression of Relapse of Disseminated Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome

Inclusion Criteria

Concurrent Medication:

Allowed:

• Vincristine, vinblastine, bleomycin, or interferon for Kaposi's sarcoma.
• Erythropoietin.
• Didanosine by exemption for 10 patients.
• Barbiturates.
• Coumarin-type anticoagulants.
• Oral contraceptives.
• Digoxin.
• Methadone.
• Narcotics.
• Acyclovir.
• Acetaminophen.
• Sulfonamides.
• Trimethoprim / sulfamethoxazole.
• Pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis.
• Topical antifungals.
• Pyrimethamine.
• Ganciclovir.
• AZT.
• Stress doses of steroids in patients with adrenal insufficiency.

Concurrent Treatment:

Allowed:

• Dose reduction or interruption of myelosuppressive therapy and transfusion to maintain hemoglobin of 7 or more g/dl.
• Radiation therapy.

Patient must:

• Show laboratory evidence of HIV infection and disseminated histoplasmosis.
• Be oriented to person, place, and time.
• Be able to give written informed consent (appropriate consent must be obtained from a parent or legal guardian for patients under 18 years of age).

Allowed:

• Abnormal liver function tests in Grade 3 toxicity range if liver biopsy shows evidence that histoplasmosis caused these abnormalities.
• Mucocutaneous candidiasis.

Prior Medication:

Allowed:

• Amphotericin B or ketoconazole for pulmonary histoplasmosis at least 3 months prior to study entry.
• Azidothymidine (AZT).
• Vincristine, vinblastine, bleomycin, or interferon for mucocutaneous Kaposi's sarcoma.
• Prophylaxis for Pneumocystis carinii pneumonia (PCP).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Severely ill, or at risk of dying from histoplasmosis within the first week of treatment, as indicated by systolic blood pressure less than 90 mm Hg , or PO2 less than 60.
• Active CNS lesions, malignancies, or infections other than MAI.
• Severe malabsorption syndrome (persistent diarrhea more than 4 weeks duration with at least 4 loose stools per day accompanied by a 10 percent or greater weight loss).
• Requiring cytotoxic therapy for malignancies.
• Any systemic fungal infection other than histoplasmosis.
• Systemic Mycobacterium avium intracellulare.
• Receiving treatment for other acute opportunistic infections whose signs and symptoms have not yet resolved or stabilized.
• History of allergy to or intolerance of imidazoles or azoles.

Concurrent Medication:

Excluded:

• All other systemic antifungal agents.
• Investigational drugs not specifically allowed.
• Oral hypoglycemics.
• Rifamycins.
• Phenytoin.
• Carbamazepine.
• Steroids in excess of physiologic replacement doses not specifically allowed.
• Cytotoxic chemotherapy.
• Discouraged:
• Antacids.
• Sucralfate.
• H2 blockers.

Patients with the following are excluded:

• Severely ill, or at risk of dying from histoplasmosis within the first week of treatment.
• Active CNS infections, malignancies or lesions not documented to be caused by histoplasmosis, which would interfere with assessment of response.
• Unable to take oral medications reliably.
• Severe malabsorption syndrome.
• Requiring cytotoxic therapy for malignancies.
• Any systemic fungal infection other than histoplasmosis.
• Systemic Mycobacterium avium intracellulare.
• Receiving treatment for other acute opportunistic infections whose signs and symptoms have not yet resolved or stabilized.

Prior Medication:

Excluded for greater than 1 week within the last 3 months:

• Fluconazole.
• Itraconazole.
• SCH 39304.
• Amphotericin B greater than 1.5 mg/kg, or any other antifungal for this episode of disseminated histoplasmosis.

Patients who the investigator feels would be undependable with regard to adherence to the protocol.

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