Inclusion Criteria

Concurrent Medication:

Allowed:

• Corticosteroids for up to 21 days at doses no greater than 20 mg/day prednisone (higher doses may be given for shorter durations, if clinically indicated).
• Zidovudine, oral contraceptives, methadone, narcotics, acyclovir, acetaminophen, sulfonamides, trimethoprim/sulfamethoxazole, pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis, topical antifungals, pyrimethamine, ganciclovir.
• Didanosine (ddI), dideoxycytidine (ddC), foscarnet, or other investigational drugs considered to be essential for patient management.

Concurrent Treatment:

Allowed:

• Transfusion.

Patients must have the following:

• HIV infection.
• Histoplasmosis.
• Appropriate consent must be obtained from a parent or legal guardian for patients less than 18 years of age.

Allowed:

• Hematologic and/or renal laboratory abnormalities.
• Concurrent malignancies.
• Concurrent infection with Mycobacteria.
• Patients with severe manifestations of histoplasmosis who are thought to be at risk of dying within one week should receive up to 250 mg amphotericin B for up to seven days prior to enrollment and then be re-evaluated. Patients who are still severely ill and do not meet eligibility criteria may not enter the study.

Specific criteria defining life-threatening histoplasmosis include:

• Systolic blood pressure < 90 mm Hg without other cause; arterial pO2 < 60 torr without other cause; and SGOT > 10 x upper limit of normal or bilirubin > 3 x upper limit of normal. Any other cases not meeting this definition must be reviewed with the protocol chair.

Prior Medication:

Allowed:

• Amphotericin B (up to 250 mg) over 7 days in patients with severe histoplasmosis.

Risk Behavior:

Allowed:

• Patients with a history of high-risk behavior for HIV infection (bisexual or homosexual men, intravenous drug abusers, recipients of blood or blood products prior to May 1985, or sexual partners of any of the foregoing).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Allergy to, or intolerance of, imidazoles or azoles.
• Active hepatitis (viral, drug induced, or other).
• Fungal infections for which the study drug is not indicated (e.g., aspergillosis, mucormycosis).
• CNS/CSF culture positive for pathogens other than H. capsulatum. If C. neoformans is subsequently identified and the patient is improving, the patient may be allowed to remain on study with the permission of the protocol chair.

Concurrent Medication:

Excluded:

• Corticosteroid use for > 21 days at > 20 mg/day of prednisone.
• Systemic antifungals.

Prior Medication:

Excluded:

• Amphotericin B at > 2.5 mg/kg for the current episode of histoplasmosis within 7 days prior to enrollment.
• Suppressive treatment for histoplasmosis or other fungal infections with > 200 mg/day of ketoconazole, fluconazole, or itraconazole, or more than 50 mg amphotericin B twice weekly.

Risk Behavior:

Excluded:

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

Patients may not have the following prior conditions:

• History of allergy to, or intolerance of, imidazoles or azoles.