TRIMETHOPRIM SULFAMETHOXAZOLE INCREMENTAL DOSE REGIMEN IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PERSONS/

Background: The mechanism of tolerance to incremental doses of trimeth oprim-sulfamethoxazole given to human immunodeficiency virus-infected persons who have had a prior intolerance to this agent has not been st udied. 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-i nduced 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 da ys to 1 double strength (DS) tablet/day in an outpatient setting. At s tudy entry, skin tests and IgG antibodies to sulfa were performed; the latter was repeated at study week 4. Results: Nineteen patients toler ated trimethoprim/sulfamethoxazole at the completion of the 8-day prot ocol (86% effective). Moderate toxicities occurred in eight persons du ring 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 stud y 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 imm unodeficiency virus-infected persons is not due to desensitization and remains undetermined.