A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS

Inclusion Criteria

Concurrent Medication:

Allowed:

• Erythropoietin.
• Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
• Immunoglobulin therapy.
• Alpha interferon.
• Patients entering study on isoniazid (INH) may continue INH therapy.
• Use of corticosteroids is discouraged. If corticosteroids are needed for the management of intracranial hypertension or cranial mass effect, use of dexamethasone is encouraged (4 g orally 4 times daily for 3 days and thereafter tapered over the next 10 to 14 days).

Patients are admitted into the study if they have:

• Laboratory evidence of HIV infection or if they have an undetermined HIV infection status if they belong to a high-risk group for HIV infection.
• Either a definite or presumptive diagnosis of toxoplasmic encephalitis. Patient or appropriate family member, or legal designee must be able to understand and sign a written informed consent.

Allowed:

• HIV encephalopathy.

AMENDED:

• Allows patients who have relapsed. Patients with a previous diagnosis of toxoplasmic encephalitis based on histopathology or documented neuroradiological response to pyrimethamine and sulfonamides or pyrimethamine and clindamycin and who have relapsed toxoplasmic encephalitis. Relapse must be documented by definite progression of lesions or appearance of new lesions compatible with toxoplasmic encephalitis.

Prior Medication:

Allowed if liver enzymes stable for 6 weeks prior to study entry:

• Rifampin.
• Isoniazid.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Infections of the central nervous system.
• Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight).
• History of sensitivity to the study medication.
• Malignancies requiring the use of cytotoxic chemotherapy.
• Coma.
• Diffuse central white matter lesions.
• Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).
• Lymphoma of the central nervous system.
• Cerebral Kaposi's sarcoma.
• Hemorrhagic diathesis or active bleeding disorder.

Concurrent Medication:

Excluded:

• Erythromycin or other macrolides.
• Sulfonamides.
• Immunomodulators.
• Cytotoxic chemotherapy.
• Amphotericin.
• Dapsone.
• Rifamycins.
• Ganciclovir.
• Allopurinol.
• Antifolates.
• Azidothymidine and other antiretrovirals and investigational agents not specifically allowed.
• Folate supplements.
• Isoniazid (INH) therapy may not be started while on therapy.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Negative HIV antibodies by a federally licensed ELISA (as determined at or after study entry), unless there is documentation of a previously positive HIV culture or p24 antigen.
• Coma.
• Diffuse central white matter lesions.
• Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).
• Lymphoma of the central nervous system.
• Cerebral Kaposi's sarcoma.
• Hemorrhagic diathesis or active bleeding disorder.
• Unable to take oral medications reliably.
• Any medical or social condition which, in the opinion of the investigator, would adversely affect either participation and/or compliance in this study.

Prior Medication:

Excluded:

• Treatment for toxoplasmic encephalitis.