PRIMARY PROPHYLAXIS WITH PYRIMETHAMINE FOR TOXOPLASMIC ENCEPHALITIS IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE - RESULTS OF A RANDOMIZED TRIAL

Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylax is for toxoplasmic encephalitis (TE) in a double-blind, randomized cli nical trial in patients with human immunodeficiency virus (HIV) diseas e, absolute CD4 lymphocyte count of <200/mu L (or prior AIDS-defining opportunistic infection), and the presence of serum Ige to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. T here was a significantly higher death rate among patients receiving py rimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1. 3-4.8; P = .006), even after adjusting for factors predictive of survi val. The TE event rate was low in both treatment groups (not significa nt). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumoc ystis carinii pneumonia developed TE (adjusted RR for the trimethoprim -sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additio nal prophylaxis for TE appears unnecessary.