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Treatment of Toxoplasmic Encephalitis in Patients with AIDS
A Randomized Trial Comparing Pyrimethamine plus Clindamycin to Pyrimethamine plus Sulfadiazine
- Brian Dannemann, MD;
- J. Allen McCutchan, MD;
- Dennis Israelski, MD;
- Diane Antoniskis, MD;
- Catherine Leport, MD;
- Benjamin Luft, MD;
- Joseph Nussbaum, MD;
- Nathan Clumeck, MD;
- Philippe Morlat, MD;
- Joseph Chiu, MD;
- Jean-Louis Vilde, MD;
- Manuel Orellana, MD;
- David Feigal, MD;
- Angie Bartok, MPH;
- Peter Heseltine, MD;
- John Leedom, MD; and
- Jack Remington, MD
Abstract
▪ Objective: To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS).
▪ Design: Randomized, unblinded phase II, multi-center trial with provision for crossover for failure or intolerance of the assigned regimen.
▪ Setting: University hospitals.
▪ Patients: Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable.
▪ Interventions: Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks.
▪ Measurements and Main Results: There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% Cl, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; Cl, 0.2 to 1.97; P > 0.2) and radiologic responses (odds ratio, 0.28; Cl, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover.
▪ Conclusions: The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.
Article and Author Information
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From Stanford University, Stanford, California; University of California, San Diego; University of Southern California, Los Angeles; Hôpital Claude Bernard, Paris, France; Hôpital Pellegrin, Bordeaux, France; State University of New York, Stony Brook; University of California, Irvine; and University of Brussels, Belgium. For current author addresses, see end of text.
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Grant Support: In part by grant AI04717 from the National Institutes of Health and grants from the California Universitywide AIDS Research Program and the Worldwide MSL Division of the Upjohn Company. Dr. Dannemann was the recipient of the CF. Aaron Endowment Fund, a fellowship grant from the Edward H. Heller Memorial Fund, and a fellowship from California Universitywide AIDS Research Program. Dr. Israelski was supported in part through a training fellowship from grant AI079089 from the National Institutes of Health and a grant from the California Universitywide AIDS Research Program.
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Requests for Reprints: J. Allen McCutchan, MD, California Collaborative Treatment Group, 8208 UCSD Medical Center, 225 Dickinson Street, San Diego, CA 92103-8208.
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Current Author Addresses: Dr. Dannemann: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, Hamilton, MT 59840.
Drs. McCutchan and Feigal and Ms. Bartok: Department of Medicine, UCSD Medical Center, 8208, 225 Dickinson Street, San Diego, CA 92103.
Dr. Israelski: Infectious Diseases Program, San Mateo County General Hospital, 222 West 39th Avenue, San Mateo, CA 94403.
Dr. Antoniskis: Northwest Permante P.C., 2701 N.W. Vaughn Street #300, Portland, OR 97217.
Drs. Nussbaum, Heseltine, and Leedom: Division of Infectious Diseases, University of Southern California Medical Center, Room 6442, 1200 N. State Street, Los Angeles, CA 90033.
Drs. Leport and Vilde: Hôpital Claude Bernard, 46 Rue Henri Huchard, 75877 Paris Cedex 18, France.
Dr. Luft: Division of Infectious Diseases, Department of Medicine, Health Science Center T-15 080, State University of New York at Stony Brook, Stony Brook, NY 11794-8153.
Dr. Clumeck: Division of Infectious Diseases, 322 Rue Haute, B1000, St. Pierre Hospital, University of Brussels, Brussels, Belgium. Dr. Morlat: Hôpital Pellegrin, place Amelie-Raba-Leon, 33 076 Bordeaux cedex, France.
Dr. Chiu: Division of Infectious Diseases, University of California, Irvine, 101 City Drive South, Route 81, Building 53, Orange, CA 92668. Dr. Orellana: Gould Medical Foundation, 600 Coffee Road, Modesto, CA 95355.
Dr. Remington: Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
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