INTERMITTENT TRIMETHOPRIM-SULFAMETHOXAZOLE COMPARED WITH DAPSONE-PYRIMETHAMINE FOR THE SIMULTANEOUS PRIMARY PROPHYLAXIS OF PNEUMOCYSTIS PNEUMONIA AND TOXOPLASMOSIS IN PATIENTS INFECTED WITH HIV

Objective: To evaluate the efficacy and safety of two oral, intermitte nt drug regimens for the simultaneous primary prophylaxis of Pneumocys tis carinii pneumonia and toxoplasmosis in patients with HIV infection . Design: Nonblinded randomized study: Patients received either 1) tri methoprim-sulfamethoxazole (160 mg-800 mg orally twice a day on a thri ce weekly regimen) or 2) 100 mg of dapsone plus 50 mg of pyrimethamine orally twice weekly. Setting: University teaching hospital in Barcelo na. Patients: 230 patients infected with HIV who had CD4 cell counts o f less than 200 x 10(6)/L and who had not previously had P. carinii pn eumonia or toxoplasmosis. Measurements: Clinical and biological evalua tions; adverse reactions; and end points of P. carinii pneumonia, toxo plasmosis, and death. Results: After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients receiving trimethoprim-sulfamethoxazole dev eloped P. carinii pneumonia (P < 0.0001). The cumulative rates of P ca rinii pneumonia at 12 and 24 months were 0% and 0% for patients receiv ing trimethoprim-sulfamethoxazole and 4% and 11% for patients receivin g dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only one epi sode of P. carinii pneumonia developed while patients were taking thes e drugs. No differences were observed for toxoplasmosis (one episode i n the trimethopri m-sulfamethoxazole arm and two in the dapsone-pyrime thamine arm), with cumulative rates at 12 and 24 months of 0% and 4% f or the trimethoprim-sulfamethoxazole arm and 2% and 7% for the dapsone -pyrimethamine arm (P = 0.65). Similar mortality rates were observed d uring follow-up (P = 0.85). Nineteen patients (9.5%) discontinued ther apy with the drugs because of adverse effects: Ten were in the trimeth oprim-sulfamethoxazole arm and 9 were in the dapsone-pyrimethamine arm (P = 0.95). Conclusions: Thrice-weekly trimethoprim-sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous primar y prophylaxis of P. carinii pneumonia and toxoplasmosis in patients in fected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a sa fe and effective alternative.