A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection

Abstract

Background. We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients in-fected with the human immunodeficiency virus (HIV). Methods. In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4 ϩ cells per cubic milli-meter received zidovudine plus one of three randomly as-signed prophylactic agents, beginning with trimethoprim– sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance. Results. The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim–sulfamethoxazole, dap-sone, and aerosolized-pentamidine groups, respectively (P ϭ 0.22). The difference in risk among treatment strate-gies was negligible in patients entering the study with 100 or more CD4 ϩ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4 ϩ cells per cubic milli-meter, the risk was 33 percent with aerosolized pentami-dine, as compared with 19 percent with trimethoprim–sul-famethoxazole and 22 percent with dapsone (P ϭ 0.04). The lowest failure rates occurred in patients receiving tri-methoprim–sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxo-plasmosis 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 surviv-al was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent. Conclusions. In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strate-gies that start with trimethoprim–sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4 ϩ lym-phocytes per cubic millimeter. (N Engl J Med 1995;332: 693-9.)