Oral Atovaquone Compared with Intravenous Pentamidine for Pneumocystis carinii Pneumonia in Patients with AIDS

1 August 1994 | Volume 121 Issue 3 | Pages 174-180

Objective: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments.

Design: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily.

Setting: Multicenter study including university and community treatment facilities.

Patients: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized.

Measurements: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued.

Results: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, –3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, –6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, –32%;CI, –48% to –17%;P < 0.001). Nine patients in each treatment group died during the study.

Conclusions: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.

Members of the Atovaquone Study Group are listed in the Appendix.

Author and Article Information

From the University of Cincinnati, Cincinnati, Ohio; the Infectious Disease Research Consortium of Georgia, Atlanta, Georgia; St. Vincent's Hospital and Medical Center, New York, New York; the Institute for HIV Research and Treatment, Davies Medical Center, San Francisco, California; Burroughs Wellcome Co., Research Triangle Park, North Carolina; Park Plaza Medical Center, Houston, Texas; the University of California, Irvine, Medical Center, Orange, California; the Research and Education Group, Portland, Oregon; Kaiser Foundation Hospital, Harbor City, California; the AIDS Clinical Research Consortium, Redwood City, California; Cedars-Sinai Medical Center, Los Angeles, California; the Regional Medical Center, Memphis, Tennessee.
Requests for Reprints: Michael N. Dohn, MD, Pulmonary/Critical Care Division, University of Cincinnati, P.O. Box 670564, Cincinnati, OH 45267-0564.
Acknowledgments: The authors thank the men and women who participated in this study and the following persons for their assistance: Joel Rosenstock, Diane Blum, Michael Thorn, Noel George, Gifford S. Leoung, Gene Mortillaro, Edward Stool, Jane Goldstein, Jarlath Black, Jeremiah G. Tilles, Bobi Keenan, Norma Martinez, Larry Rick, Cliff Chen, Brian Camp, Debbie Claire, Debra Ray, Nancy Pietroski, Eileen Cushid, Joyce Amann, Michael Baker, Wendie Lubin, Joan E. Wilson, Beverly Heinze-Lacey, Ellen Godfrey, Teri Flynn, Vel Sivapalan, Jamie Carroll, and Ann Johiro.
Grant Support: By the Burroughs Wellcome Co.