Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Dapsone and pentamidine were equally effective for preventing Pneumocystis carinii pneumonia

ACP J Club. 1994 May-June;120:69. doi:10.7326/ACPJC-1994-120-3-069


Source Citation

Torres RA, Barr M, Thorn M, et al. Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. Am J Med. 1993 Dec;95:573-83.


Abstract

Objective

To compare the effectiveness of aerosolized pentamidine with dapsone for the prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and CD4+ lymphocyte counts < 250/mm3.

Design

Randomized controlled trial with a mean follow-up of 43 weeks.

Setting

Clinics for HIV patients, homosexual men and women, and homeless men, and private physicians' offices in New York City.

Patients

298 patients (mean age 38 y, 94% men) seropositive for HIV with a past episode of PCP or a diagnosis of the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) and a CD4+ lymphocyte count < 250/mm3. Exclusion criteria were age < 18 years; preexisting pulmonary disease; abnormal renal, liver, or hematologic function; or glucose 6-phosphate dehydrogenase deficiency. 20 patients never received drug therapy and were excluded from the analysis. The presence of Toxoplasma antibody was not determined.

Intervention

126 patients received dapsone, 100 mg 2 times/wk, and 152 patients received pentamidine isethionate by nebulizer, 100 mg once a week for 4 weeks, then 100 mg every 2 weeks.

Main outcome measures

PCP, toxoplasmic encephalitis, death, and adverse effects.

Main results

An intention-to-treat analysis showed no difference in PCP occurrence rates between patients receiving aerosolized pentamidine (15 patients) and those receiving dapsone (15 patients) (10% vs 12%, P > 0.2). No difference in PCP-free survival existed (59% vs 56%, P = 0.4). Primary prophylaxis for PCP was more effective than secondary prophylaxis with either drug (P < 0.001). In both treatment groups, zidovudine users remained free of PCP longer than non-zidovudine users (P < 0.001). 6 patients in the aerosolized pentamidine group developed new episodes of toxoplasmic encephalitis compared with no patients in the dapsone group (P = 0.01). No difference was shown in the Toxoplasma-free survival after 12 months between the 2 groups. Aerosolized pentamidine was withdrawn in 3 patients (2%) because of bronchospasm, whereas dapsone was withdrawn in 14 patients (11%) because of skin rash, hepatitis, or hemolytic anemia.

Conclusions

Dapsone was as effective as aerosolized pentamidine in preventing Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection and CD4+ lymphocyte counts < 250/mm3 Fewer new cases of toxoplasmic encephalitis occurred among the group receiving dapsone than among those receiving aerosolized pentamidine but no difference was shown for 12-month Toxoplasma-free survival.

Source of funding: Samuel and May Rudin Foundation, Inc.

For article reprint: Dr. R.A. Torres, AIDS Center, St. Vincent's Hospital and Medical Center, 153 West 11th Street, New York, NY 10011, USA. FAX 212-353-3056.


Commentary

The results of the study of Torres and colleagues confirm the role of intermittent-dose dapsone (100 mg twice weekly) as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) or aerosolized pentamidine for PCP prophylaxis and raise the possibility that dapsone alone may also prevent toxoplasmosis. Ideally, the efficacy of any agent to prevent toxoplasmosis should be tested in a cohort with known Toxoplasma antibody status. The combination of dapsone (50 mg/d) plus pyrimethamine (50 mg/wk) was superior to aerosolized pentamidine in 262 patients with serologic evidence of previous exposure to Toxoplasma (1). Lower rates of toxoplasmosis have also been identified in recipients of TMP-SMX compared with recipients of aerosolized pentamidine in a randomized study of PCP prophylaxis; however, this study did not include data on Toxoplasma antibody status (2). Unless the efficacy of dapsone alone can be confirmed in another randomized trial of PCP prophylaxis, ideally in a cohort with known Toxoplasma antibody status, either TMP-SMX or the combination of dapsone and pyrimethamine should be favored in clinical practice for use in patients at risk for both PCP and toxoplasmosis. However, with the decrease in the incidence of these infections in HIV disease, we are not likely to ever be able to do this trial.

Judith S. Currier, MD, MSc
University of Southern CaliforniaLos Angeles, California, USA


References

1. Girard PM, Landman R, Gaudebout C, et al. Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group. N Engl J Med. 1993;328:1514-20.

2. Hardy WD, Feinberg J, Finkelstein DM, et al. 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. N Engl J Med. 1992;327:1842-8.


Editor's Note

A meta-analysis by Ioannidis and colleagues (3) showed that SMP-TMX was the superior regimen for P. carinii prophylaxis in patients with HIV infection. Low doses improved drug tolerance without losing effectiveness.

3. Ioannidis JP, Cappelleri JC, Skolnik PR, Lau J, Sacks HS. A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med. 1996;156:177-88.