A Controlled Trial of Trimethoprim–Sulfamethoxazole or Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: AIDS Clinical Trials Group Protocol 021

W. David Hardy, Judith Feinberg, Dianne M. Finkelstein, Maureen E. Power, Weili he, Carolyn Kaczka, Peter T. Frame, Martin Holmes, Hetty Waskin, Robert J. Fass, William G. Powderly, Roy T. Steigbigel, Abigail Zuger, Robert S. Holzman

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Abstract

Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim–sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. In the trimethoprim–sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim–sulfamethoxazole and 27.6 percent with pentamidine (P<0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P<0.001; 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim–sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim–sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim–sulfamethoxazole (P = 0.017). In patients with AIDS who are receiving zidovudine, trimethoprim–sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection. (N Engl J Med 1992;327:1842–8.), PNEUMOCYSTIS CARINII pneumonia (PCP) is the most common opportunistic infection used to establish a diagnosis of the acquired immunodeficiency syndrome (AIDS).1 PCP exacts a considerable toll in mortality, morbidity, and expense,2 and recurrences are common without prophylaxis.3 Trimethoprim–sulfamethoxazole,4 , 5 aerosolized pentamidine,6 dapsone,7 and pyrimethamine—sulfadoxine (Fansidar)8 have all been used to prevent PCP in AIDS; however, no definitive comparative study has been reported. We compared the safety and efficacy of trimethoprim–sulfamethoxazole and aerosolized pentamidine as prophylaxis against pneumocystosis in patients with AIDS after recovery from an initial episode of PCP. The trial was conducted at 23 sites of the AIDS Clinical Trials…

Original languageEnglish
Pages (from-to)1842-1848
Number of pages7
JournalNew England Journal of Medicine
Volume327
Issue number26
DOIs
StatePublished - Dec 24 1992

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