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Reduced Toxicity With Gradual Initiation of Trimethoprim-Sulfamethoxazole as Primary Prophylaxis forPneumocystis cariniiPneumonia: AIDS Clinical Trials Group 268

Para Michael F.; Finkelstein, Dianne; Becker, Simone; Dohn, Michael; Walawander, Ann; Black, John R.; the AIDS Clinical Trials Group 268 Study Team
JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2000

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1infected study subjects with a CD4+ cell count <250 × 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p = .0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

Address correspondence and reprint requests to Michael F. Para, Ohio State University ACTU, University Hospitals Clinic, Room 4725, 456 West 10th Avenue, Columbus, OH 43210, U.S.A.; email:

This work was presented in part at the 4th Conference on Retroviruses and Opportunistic Infections [abstract #2], Washington, DC, January 1997.

Manuscript received January 24, 2000; accepted March 28, 2000.

© 2000 Lippincott Williams & Wilkins, Inc.