Dapsone/pyrimethamine may prevent mycobacterial disease in immunosuppressed patients infected with the human immunodeficiency virus

Dapsone exhibits activity against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) in vitro. We retrospectively examined the incidence of mycobacterial diseases within a randomized prospective trial of prophylaxis for Pneumocystis carinii pneumonia and toxoplasmosis. Of 501 participants who had not previously had a mycobacterial disease, 274 received dapsone/pyrimethamine (200/75 mg once weekly) and 227 received aerosolized pentamidine (300 mg once every 4 weeks). The median CD4 lymphocyte count was 113/μL, and the median duration of treatment was 369 days. Six cases of tuberculosis, 22 of MAC infection, and 3 of Mycobacterium genavense disease occurred during treatment. Stratified by baseline CD4 lymphocyte counts, the annual product-limit incidence of mycobacterial disease was 5% during treatment with dapsone/pyrimethamine vs. 12% during treatment with aerosolized pentamidine for patients whose counts were 0–24/μL, 0 vs. 12% for those whose counts were 25–49/μL, and 7% vs. 9% for those whose counts were 50–99/μL. Adjusted for CD4 lymphocyte counts at start of treatment, the relative risk for patients receiving dapsone/pyrimethamine was 0.47 (95% confidence interval, 0.19–1.16; P =.10). This inexpensive and simple regimen may prevent mycobacterial diseases and warrants further investigation as a means of prophylaxis for multiple opportunistic diseases.