title: Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials Group 268.
abstract: 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-1-infected study subjects with a CD4+ cell count <250 x 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.
authors.affiliation: Division of Infectious Disease, The Ohio State University, Columbus, Ohio, USA. para.1.osu.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Para
authors.forename: D
authors.initials: D
authors.lastname: Finkelstein
authors.forename: S
authors.initials: S
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Dohn
authors.forename: A
authors.initials: A
authors.lastname: Walawander
authors.forename: J R
authors.initials: JR
authors.lastname: Black
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D005334:Fever / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011537:Pruritus / Q000139:chemically induced; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination