Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both

Wafaa M. El-Sadr, Robert L. Murphy, Teresa McCabe Yurik, Roberta Luskin-Hawk, Tony W. Cheung, Henry H. Balfour, Robert Eng, Thomas Hooton, Thomas M. Kerkering, Malte Schutz, Charles D. Van Der Horst, Richard Hafner

Research output: Contribution to journalArticle

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Abstract

Background: Although trimethoprim-sulfameth-oxazole is the drug of choice of the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. Methods: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500 mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. Results: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P>0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). Conclusions: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

Original languageEnglish
Pages (from-to)1889-1895
Number of pages7
JournalNew England Journal of Medicine
Volume339
Issue number26
DOIs
StatePublished - Dec 24 1998
Externally publishedYes

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Atovaquone
Dapsone
Trimethoprim
Pneumocystis Pneumonia
Sulfonamides
HIV Infections
Confidence Intervals
Sulfamethoxazole Drug Combination Trimethoprim
Oxazoles
Suspensions
HIV

ASJC Scopus subject areas

  • Medicine(all)

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Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. / El-Sadr, Wafaa M.; Murphy, Robert L.; Yurik, Teresa McCabe; Luskin-Hawk, Roberta; Cheung, Tony W.; Balfour, Henry H.; Eng, Robert; Hooton, Thomas; Kerkering, Thomas M.; Schutz, Malte; Van Der Horst, Charles D.; Hafner, Richard.

In: New England Journal of Medicine, Vol. 339, No. 26, 24.12.1998, p. 1889-1895.

Research output: Contribution to journalArticle

El-Sadr, WM, Murphy, RL, Yurik, TM, Luskin-Hawk, R, Cheung, TW, Balfour, HH, Eng, R, Hooton, T, Kerkering, TM, Schutz, M, Van Der Horst, CD & Hafner, R 1998, 'Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both', New England Journal of Medicine, vol. 339, no. 26, pp. 1889-1895. https://doi.org/10.1056/NEJM199812243392604
El-Sadr, Wafaa M. ; Murphy, Robert L. ; Yurik, Teresa McCabe ; Luskin-Hawk, Roberta ; Cheung, Tony W. ; Balfour, Henry H. ; Eng, Robert ; Hooton, Thomas ; Kerkering, Thomas M. ; Schutz, Malte ; Van Der Horst, Charles D. ; Hafner, Richard. / Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. In: New England Journal of Medicine. 1998 ; Vol. 339, No. 26. pp. 1889-1895.
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abstract = "Background: Although trimethoprim-sulfameth-oxazole is the drug of choice of the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. Methods: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500 mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. Results: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P>0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). Conclusions: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.",
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T1 - Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both

AU - El-Sadr, Wafaa M.

AU - Murphy, Robert L.

AU - Yurik, Teresa McCabe

AU - Luskin-Hawk, Roberta

AU - Cheung, Tony W.

AU - Balfour, Henry H.

AU - Eng, Robert

AU - Hooton, Thomas

AU - Kerkering, Thomas M.

AU - Schutz, Malte

AU - Van Der Horst, Charles D.

AU - Hafner, Richard

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N2 - Background: Although trimethoprim-sulfameth-oxazole is the drug of choice of the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. Methods: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500 mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. Results: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P>0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). Conclusions: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

AB - Background: Although trimethoprim-sulfameth-oxazole is the drug of choice of the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. Methods: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500 mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. Results: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P>0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). Conclusions: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

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