title: Trimethoprim/sulfamethoxazole incremental dose regimen in human immunodeficiency virus-infected persons.
abstract: BACKGROUND
  The mechanism of tolerance to incremental doses of trimethoprim-sulfamethoxazole given to human immunodeficiency virus-infected persons who have had a prior intolerance to this agent has not been studied.
  
  
  OBJECTIVE
  We prospectively evaluated a regimen of incremental doses of oral trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected persons who had a prior trimethoprim-sulfamethoxazole-induced fever and nonexfoliative skin rash to investigate the mechanism by which it permits tolerance.
  
  
  METHODS
  Oral trimethoprim (0.00004 mg)/sulfamethoxazole (0.00002 mg) was given to 22 human immunodeficiency virus-infected persons on day 1 and gradually increased over eight days to 1 double strength (DS) tablet/day in an outpatient setting. At study entry, skin tests and IgG antibodies to sulfa were performed; the latter was repeated at study week 4.
  
  
  RESULTS
  Nineteen patients tolerated trimethoprim/sulfamethoxazole at the completion of the 8-day protocol (86% effective). Moderate toxicities occurred in eight persons during the desensitization protocol; five of these were able to continue trimethoprim/sulfamethoxazole with adjunctive prednisone. Skin tests to sulfa antigen were negative in all persons. Eleven patients at study entry had antibodies to sulfamethoxazole; IgG antibodies appeared at week 4 in 8 of the 11 patients who initially had no antibody detected.
  
  
  CONCLUSIONS
  The mechanism of tolerance to the incremental doses of trimethoprim/sulfamethoxazole given to previously intolerant human immunodeficiency virus-infected persons is not due to desensitization and remains undetermined.
authors.affiliation: Department of Medicine, University of Michigan Medical Ctr, Ann Arbor 48109-0378, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Rich
authors.forename: T
authors.initials: T
authors.lastname: Sullivan
authors.forename: D
authors.initials: D
authors.lastname: Greineder
authors.forename: P H
authors.initials: PH
authors.lastname: Kazanjian
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D004361:Drug Tolerance; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000008:administration & dosage* / Q000009:adverse effects; D014295:Trimethoprim / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014295:Trimethoprim; D013420:Sulfamethoxazole