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Trimethoprim/sulfamethoxazole incremental dose regimen in human immunodeficiency virus-infected persons
J D Rich1, T Sullivan, D Greineder
1Department of Medicine, University of Michigan Medical Ctr, Ann Arbor 48109-0378, USA.
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.