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.