A METAANALYSIS OF THE RELATIVE EFFICACY AND TOXICITY OF PNEUMOCYSTIS-CARINII PROPHYLACTIC REGIMENS

Background: Finding the optimal strategy for Pneumocystis carinii prop hylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their r elative efficacy and tolerance are not well understood. Methods: A met a-analysis overviewed 35 randomized trials comparing different regimen s for P carinii prophylaxis directly or with placebo. Analyses were ba sed on intention-to-treat. On-treatment data were also analyzed when a vailable. Results: Regardless of dose, sulfamethoxazole-trimethoprim w as almost universally effective for patients who tolerated it. The ris k of discontinuing sulfamethoxazole-trimethoprim because of side effec ts decreased by 43% (95% confidence interval, 30% to 54%) if one doubl e-strength tablet was given three times. week instead of daily. For da psone, among 100 patients given 100 mg daily instead of twice a week f or 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose use d. Prophylaxis failures might be halved if the dose of aerosolized pen tamidine were doubled. Compared with aerosolized pentamidine, oral reg imens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasm osis events by on-treatment analysis, but only 33% (95% confidence int erval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens. Conclusions: S ulfamethoxazole-trimethoprim is the superior regimen, and low doses co uld improve tolerance without losing effectiveness for primary prophyl axis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regi mens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is i nadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventi ng toxoplasmosis.