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).

Condition	Treatment or Intervention
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine

Further Study Details: 

Expected Total Enrollment:  600

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

California
      Community Consortium of San Francisco, San Francisco,  California,  94110,  United States
Colorado
      Denver CPCRA / Denver Public Hlth, Denver,  Colorado,  802044507,  United States
Connecticut
      Hill Health Corp, New Haven,  Connecticut,  06519,  United States
Delaware
      Wilmington Hosp / Med Ctr of Delaware, Wilmington,  Delaware,  19899,  United States
Georgia
      AIDS Research Consortium of Atlanta, Atlanta,  Georgia,  30308,  United States
Illinois
      AIDS Research Alliance - Chicago, Chicago,  Illinois,  60657,  United States
Louisiana
      Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans,  Louisiana,  70112,  United States
Michigan
      Henry Ford Hosp, Detroit,  Michigan,  48202,  United States
      Comprehensive AIDS Alliance of Detroit, Detroit,  Michigan,  48201,  United States
New Jersey
      North Jersey Community Research Initiative, Newark,  New Jersey,  071032842,  United States
New York
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10456,  United States
      Clinical Directors Network of Region II, New York,  New York,  10011,  United States
      Addiction Research and Treatment Corp, Brooklyn,  New York,  11201,  United States
Oregon
      Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland,  Oregon,  972109951,  United States
Virginia
      Richmond AIDS Consortium, Richmond,  Virginia,  23298,  United States

Study chairs or principal investigators

Jacobson M,  Study Chair
Besch CL,  Study Chair

Study ID Numbers:  CPCRA 001
Record last reviewed:  November 1998
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000666
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08