A Study of Amphotericin B in the Treatment of Fungal Infections of the Mouth in HIV-Infected Patients Who Have Not Had Success With Fluconazole

A Phase II Trial of Amphotericin B Oral Suspension for Fluconazole-Resistant Oral Candidiasis in HIV-Infected Patients

To assess response and toxicity in patients with fluconazole-resistant oral candidiasis ( thrush ) when given initial induction with amphotericin B oral suspension.

Experience with amphotericin B oral suspension for drug-sensitive thrush in HIV-infected patients is limited but encouraging.

Experience with amphotericin B oral suspension for drug-sensitive thrush in HIV-infected patients is limited but encouraging.

Patients swish and swallow amphotericin B oral suspension after each meal and at bedtime for 14 days, at which time they are deemed a responder, nonresponder, or failure to induction therapy. Responders receive maintenance twice daily, while nonresponders receive 14 further days of initial induction. Failures discontinue the study. Responders after 28 days of induction are placed on maintenance. After successful completion of initial induction, patients remain on study for 6 months.

Inclusion Criteria

Patients must have:

• HIV infection OR diagnosis of AIDS.
• Diffuse oral candidiasis, symptomatic or asymptomatic, that is resistant to fluconazole.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Current symptoms of esophageal candidiasis unless there are negative endoscopic visualization and biopsy for Candida or related yeasts.
• Perioral lesions only (e.g., angular stomatitis, perleche).
• Inability to swish and swallow oral solution.
• Inability to tolerate further oral therapy for thrush.

Concurrent Medication:

Excluded:

• Fluconazole.
• Itraconazole.
• Ketoconazole.
• Flucytosine.
• Intravenous amphotericin or other non-study formulations.
• Nystatin.
• Clotrimazole.
• Other investigational antifungal agents.
• Systemic cytotoxic chemotherapy for malignancy.

Concurrent Treatment:

Excluded:

• Radiation therapy to the mouth, neck, or chest.

Patients with the following prior conditions are excluded:

• Esophageal candidiasis, proven or presumptive, occurring since fluconazole failure.
• Successful treatment of thrush with fluconazole at <= 200 mg/day after original treatment failure.
• History of oral candidiasis that recurred or persisted despite IV amphotericin B given once or more weekly.
• History of anaphylaxis to amphotericin B.
• History of hypersensitivity to components in amphotericin B oral suspension.

Prior Medication:

Excluded within 6 weeks prior to study entry:

• Cytotoxic therapy for malignancy.
• Corticosteroids at higher than replacement doses.