Pyrimethamine alone as prophylaxis for cerebral toxoplasmosis in patients with advanced HIV infection

Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients were at high risk for toxoplasma encephalitis (CD4+ counts < or = 200/microliter, and presence of serum IgG antibodies to Toxoplasma gondii). The overall treatment period was 697 months (mean 12.5 +/- 12.1). During prophylaxis, only one patient developed toxoplasma encephalitis, four patients discontinued treatment due to adverse reactions. Steady state pyrimethamine plasma concentrations were measured by gas chromatography. Mean plasma level was 1,887 +/- 1,161 ng/ml, during liver enzyme-inducing comedication plasma levels were significantly (p = 0.0001) reduced (1,488 +/- 884 ng/ml versus 1,978 +/- 1,196 ng/ml without comedication). All patients received a folinic acid supplement of 7.5 mg daily. Serum folate levels ranged from 5.7-105 (43.7 +/- 29.2) nmol/l; severe hematological side effects did not occur.