A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens

Background: Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be 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 different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to- treat. On-treatment data were also analyzed when available. Results: Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 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 used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens. Conclusions: Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. 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 regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.