Official Title: “A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection”

To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii.

Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine.

Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).

Study Type: Interventional

Study Design: Prevention, Parallel Assignment

Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine.

Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).

Patients are randomized to receive pyrimethamine or placebo three times a week. All patients must be on aerosolized pentamidine, trimethoprim / sulfamethoxazole (T/S), or dapsone for Pneumocystis carinii pneumonia prophylaxis. Patients will be evaluated bi-weekly for the first month and every other month thereafter for at least 24 months.

Intervention(s) in this Clinical Trial

• Drug: Pyrimethamine

Inclusion Criteria

Concurrent Medication:

Required:

• Prophylactic treatment for Pneumocystis carinii pneumonia with aerosolized pentamidine, dapsone, or trimethoprim / sulfamethoxazole.

Allowed:

• Most medications not specifically excluded.

Prior Medication:

Allowed:

• Antivirals.
• Antiretrovirals.

Patients:

• Must be HIV positive or have an AIDS-defining illness OR be at known risk for HIV infection and have a CD4 cell count < 200/mm3 and no other known immunosuppressive disease.
• Must have positive titer for Toxoplasma gondii.
• Must be or become a patient of a CPCRA physician.
• May participate in other clinical trials as long as there is no potential activity against Toxoplasma gondii or cross-toxicity among study drugs.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• History of ocular, pulmonary, or central nervous system (CNS) toxicity.
• CNS lesions.
• Neurologic deficits except peripheral neuropathy.
• Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting.
• Sensitivity to pyrimethamine.

Concurrent Medication:

Excluded:

• On-going therapy with clindamycin, fansidar, methotrexate, trimetrexate, spiramycin, azithromycin, clarithromycin, 566C80, and/or sulfa agents other than anti-PCP agents.

Patients with the following are excluded:

• History of ocular, pulmonary, or central nervous system (CNS) toxicity.
• CNS lesions or history of CNS lesions.
• Neurologic deficits except peripheral neuropathy.
• Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting.
• Sensitivity to pyrimethamine.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Jacobson M Study Chair   

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000666

Study ID Number: CPCRA 001

ClinicalTrials.gov Identifier: NCT00000666

Health Authority: United States: Federal Government