A RANDOMIZED TRIAL OF 3 ANTIPNEUMOCYSTIS AGENTS IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Background. We evaluated the effectiveness of three treatment strategi es for the prevention of a first episode of Pneumocystis carinii pneum onia in patients infected with the human immunodeficiency virus (HIV). Methods. In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plu s one of three randomly assigned prophylactic agents, beginning with t rimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of i ntolerance. Results. The estimated 36-month cumulative risks of P. car inii pneumonia were 18 percent, 17 percent, and 21 percent in the trim ethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups , respectively (P = 0.22). The difference in risk among treatment stra tegies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer th an 100 CD4+ cells per cubic millimeter, the risk was 33 percent with a erosolized pentamidine, as compared with 19 percent with trimethoprim- sulfamethoxazole and 22 percent with dapsone (P=0.04). The lowest fail ure rates occurred in patients receiving trimethoprim-sulfamethoxazole , acid failures were more common with 50 mg of dapsone than with 100 m g. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, a nd the mortality attributable to P. carinii pneumonia was only 1 perce nt. Conclusions. In patients with advanced HIV infection, the three tr eatment strategies we examined have similar effectiveness in preventin g P. carinii pneumonia. Strategies that start with trimethoprim-sulfam ethoxazole or with high-dose dapsone, rather than aerosolized pentamid ine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.