Trimethoprim/sulfamethoxazole incremental dose regimen in human immunodeficiency virus-infected persons.
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.
Rich
J D
JD
Department of Medicine, University of Michigan Medical Ctr, Ann Arbor 48109-0378, USA.
Sullivan
T
T
Greineder
D
D
Kazanjian
P H
PH
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
D014295:Trimethoprim; D013420:Sulfamethoxazole