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. ACTG 108 Study Group.
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.


METHODS
A randomized, double-blind study.


METHODS
24 U.S. academic medical centers.


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


METHODS
Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone.


METHODS
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>.02). 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.
Safrin
S
S
San Francisco General Hospital, San Francisco, CA 94110.
Finkelstein
D M
DM
Feinberg
J
J
Frame
P
P
Simpson
G
G
Wu
A
A
Cheung
T
T
Soeiro
R
R
Hojczyk
P
P
Black
J R
JR
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002981:Clindamycin / Q000009:adverse effects / Q000627:therapeutic use*; D003622:Dapsone / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011319:Primaquine / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D011319:Primaquine