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A dose-response meta-analysis of Pneumocystis carinii prophylaxis.
Ioannidis JP; Cappelleri JC; Skolnik PR; Lau J; Sacks HS; New England
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:159. Unique

We performed a meta-analysis of 35 randomized control trials with 6,583 patients comparing different regimens for P. carinii prophylaxis to assess dose-responses for the efficacy and toxicity of these regimens. Estimates were calculated with random and fixed effects models, weighted rates, and dose-response meta-regressions. Regardless of dose, trimethoprim/sulfamethoxazole (TMP/SMX) was almost universally effective for patients who tolerate it. Discontinuations of TMP/SMX due to side effects decreased by 43% (95% CI, 30- 54%) by dosing three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for a year (primary prophylaxis), 7 fewer would develop PCP, but 17 more would have significant toxicity. Aerosolized pentamidine (AP) was well tolerated regardless of the dose used and failures might be halved if the dose was doubled. Compared with AP, oral regimens prevented 73% (95% CI, 57- 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% CI, 12- 50%) by intention-to-treat. There was no difference in mortality between prophylactic regimens. Overall, TMP/SMX is the superior regimen and is better tolerated at low doses. Low doses of dapsone reduce toxicity, but some efficacy is lost. There are few data on low-dose regimens in secondary prophylaxis. AP is inadequate for toxoplasmosis prevention and strategies which improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis. as most cases occur when oral therapy has been discontinued.

Acquired Immunodeficiency Syndrome/*COMPLICATIONS Dapsone/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Dose-Response Relationship, Drug Human Pentamidine/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE Pneumonia, Pneumocystis carinii/COMPLICATIONS/*PREVENTION & CONTROL Toxoplasmosis/PREVENTION & CONTROL Trimethoprim-Sulfamethoxazole Combination/ADMINISTRATION & DOSAGE/ *THERAPEUTIC USE ABSTRACT