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Intermittent Trimethoprim-Sulfamethoxazole Compared with Dapsone-Pyrimethamine for the Simultaneous Primary Prophylaxis of Pneumocystis Pneumonia and Toxoplasmosis in Patients Infected with HIV

Daniel Podzamczer, MD; Albert Salazar, MD; Josep Jimenez, MD; Ezequiel Consiglio, MD; Miguel Santin, MD; Aurora Casanova, MD; Gabriel Rufi, MD; and Francisco Gudiol, MD
[+] Article and Author Information

From Ciutat Sanitaria de Bellvitge, University of Barcelona, Barcelona, Spain. Requests for Reprints: Daniel Podzamczer, MD, Infectious Disease Service, Ciutat Sanitaria de Bellvitge, c/Feixa Llarga s/n, L'Hospitalet, 08907 Barcelona, Spain. Grant Support: In part by grant FISS 91/0469 from the Fondo de Investigacion de la Seguridad Social.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;122(10):755-761. doi:10.7326/0003-4819-122-10-199505150-00004
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Objective: To evaluate the efficacy and safety of two oral, intermittent drug regimens for the simultaneous primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with HIV infection.

Design: Nonblinded randomized study: Patients received either 1) trimethoprim-sulfamethoxazole [160 mg-800 mg orally twice a day on a thrice weekly regimen] or 2) 100 mg of dapsone plus 50 mg of pyrimethamine orally twice weekly.

Setting: University teaching hospital in Barcelona.

Patients: 230 patients infected with HIV who had CD4 cell counts of less than 200 × 106/L and who had not previously had P. carinii pneumonia or toxoplasmosis.

Measurements: Clinical and biological evaluations; adverse reactions; and end points of P. carinii pneumonia, toxoplasmosis, and death.

Results: After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients receiving trimethoprim-sulfamethoxazole developed P. carinii pneumonia (P < 0.0001). The cumulative rates of P. carinii pneumonia at 12 and 24 months were 0% and 0% for patients receiving trimethoprim-sulfamethoxazole and 4% and 11% for patients receiving dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only one episode of P. carinii pneumonia developed while patients were taking these drugs. No differences were observed for toxoplasmosis (one episode in the trimethoprim-sulfamethoxazole arm and two in the dapsone-pyrimethamine arm), with cumulative rates at 12 and 24 months of 0% and 4% for the trimethoprim-sulfamethoxazole arm and 2% and 7% for the dapsone-pyrimethamine arm (P = 0.65). Similar mortality rates were observed during follow-up (P = 0.85). Nineteen patients (9.5%) discontinued therapy with the drugs because of adverse effects: Ten were in the trimethoprim-sulfamethoxazole arm and 9 were in the dapsone-pyrimethamine arm (P = 0.95).

Conclusions: Thrice-weekly trimethoprim-sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous primary prophylaxis of P. carinii pneumonia and toxoplasmosis in patients infected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a safe and effective alternative.

Figures

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Figure 1.
Cumulative rates of Pneumocystis carinii pneumonia according to prophylaxis regimen (Kaplan-Meier product-limit estimates).Pneumocystis carinii

DP = dapsone-pyrimethamine; PCP = pneumonia; TMP-SMX = trimethoprim-sulfamethoxazole (cotrimoxazole).

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Figure 2.
Cumulative rates of toxoplasmosis in patients seropositive for Toxoplasma gondii according to prophylaxis regimen.

(Kaplan-Meier product-limit estimates). DP = dapsone-pyrimethamine; TMP-SMX = trimethoprim-sulfamethoxazole (co-trimoxazole).

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