A Meta-analysis of the Relative Efficacy and Toxicity of Pneumocystis carinii Prophylactic Regimens

doi:10.1001/archinte.1996.00440020081010

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Vol. 156 No. 2, 22 JANUARY 1996

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A Meta-analysis of the Relative Efficacy and Toxicity of Pneumocystis carinii Prophylactic Regimens

John P. A. Ioannidis, MD; Joseph C. Cappelleri, PhD, MPH; Paul R. Skolnik, MD; Joseph Lau, MD; Henry S. Sacks, PhD, MD

Arch Intern Med. 1996;156(2):177-188.

Abstract

Background
Finding the optimal strategy for Pneumocystis carinii prophylaxisin patients with human immunodeficiency virus infection canbe problematic. Several prophylactic regimens are available,but their relative efficacy and tolerance are not well understood.

Methods
A meta-analysis overviewed 35 randomized trials comparing differentregimens for P carinii prophylaxis directly or with placebo.Analyses were based on intention-to-treat. On-treatment datawere also analyzed when available.

Results
Regardless of dose, sulfamethoxazole-trimethoprim was almostuniversally effective for patients who tolerated it. The riskof discontinuing sulfamethoxazole-trimethoprim because of sideeffects decreased by 43% (95% confidence interval, 30% to 54%)if one double-strength tablet was given three times a week insteadof daily. For dapsone, among 100 patients given 100 mg dailyinstead of twice a week for 1 year (primary prophylaxis), sevenfewer patients would develop P carinii pneumonia, but 17 morewould have significant toxic reactions. Aerosolized pentamidinewas well tolerated regardless of the dose used. Prophylaxisfailures might be halved if the dose of aerosolized pentamidinewere doubled. Compared with aerosolized pentamidine, oral regimensprevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosisevents by on-treatment analysis, but only 33% (95% confidenceinterval, 12% to 50%) by intention-to-treat. No significantdifference in mortality was demonstrated between different regimens.

Conclusions
Sulfamethoxazole-trimethoprim is the superior regimen, and lowdoses could improve tolerance without losing effectiveness forprimary prophylaxis. Low doses of dapsone reduce toxic effects,but at the expense of some loss of efficacy. There are few dataon the use of low-dose regimens for secondary prophylaxis. Highdoses of aerosolized pentamidine may improve the efficacy ofthis regimen. Aerosolized pentamidine is inadequate for preventionof toxoplasmosis, and strategies that improve the toleranceof oral regimens may increase effectiveness in preventing toxoplasmosis.

(Arch Intern Med. 1996;156:177-188)

Author Affiliations

From the Division of Geographic Medicine and Infectious Diseases (Drs Ioannidis and Skolnik) and the Division of Clinical Care Research (Drs Cappelleri and Lau), New England Medical Center Hospitals, Boston, Mass; and Departments of Medicine and Community Medicine and the Thomas C. Chalmers Clinical Trials Unit, Mount Sinai School of Medicine, New York, NY (Dr Sacks).

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