Comparison of Three Regimens for Treatment of Mild to Moderate Pneumocystis carinii Pneumonia in Patients with AIDS: A Double-Blind, Randomized Trial of Oral Trimethoprim-Sulfamethoxazole, Dapsone-Trimethoprim, and Clindamycin-Primaquine

1 May 1996 | Volume 124 Issue 9 | Pages 792-802

Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.

Design: A randomized, double-blind study.

Setting: 24 U.S. academic medical centers.

Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO₂-PaO₂) of 45 mm Hg or less.

Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO (₂-PaO)₂ of 35 to 45 mm Hg at study entry also received prednisone.

Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO₂-PaO₂ of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions.

Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P = 0.2), therapeutic failure (P > 0.2), or a complete course of therapy (P > 0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P > 0.2). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P = 0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P = 0.01).

Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

Author and Article Information

From University of California, San Francisco, San Francisco, California; Harvard School of Public Health, Boston, Massachusetts; Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Cincinnati College of Medicine, Cincinnati, Ohio; Harbor-UCLA Medical Center, Torrance, California; Mount Sinai Medical Center and Albert Einstein College of Medicine, New York, New York; Frontier Science Technology and Research Foundation, Amherst, New York; and Methodist Hospital of Indiana, Indianapolis, Indiana.
Acknowledgments: The authors thank Drs. John Mills, Fred Sattler, and Sam Bozzette for consultation in the design and performance of this trial. They also thank the patients who participated in the trial.
Grant Support: By grants from the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and the General Clinical Research Units of the National Center for Research Resources and Agency for Health Care Policy and Research grant HS07824.
Requests for Reprints: Sharon Safrin, MD, San Francisco General Hospital, Building 80, Ward 84, San Francisco, CA 94110.
Current Author Addresses: Dr. Safrin: San Francisco General Hospital, Building 80, Ward 84, San Francisco, CA 94110.