Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.
We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.
Stein
D S
DS
Department of Medicine, University of Tennessee, Memphis.
Stevens
R C
RC
Terry
D
D
Laizure
S C
SC
Palte
S
S
Lancaster
D J
DJ
Weems
J J
JJ
Williams
C L
CL
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003181:Complement C4 / Q000302:isolation & purification; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011446:Prospective Studies; D013420:Sulfamethoxazole / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood; D014295:Trimethoprim / Q000008:administration & dosage* / Q000097:blood; D015215:Zidovudine / Q000627:therapeutic use
D003181:Complement C4; C021282:N(4)-acetylsulfamethoxazole; D015215:Zidovudine; D014295:Trimethoprim; D013420:Sulfamethoxazole; D002955:Leucovorin