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J Clin Pharmacol. 1999 May;39(5):533-7.

The association of opportunistic infections with the occurrence of trimethoprim/sulfamethoxazole hypersensitivity in patients infected with human immunodeficiency virus.

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  • 1Department of Medicine, School of Medicine, SUNY Health Science Center at Syracuse, New York 13210, USA.


Hypersensitivity from trimethoprim/sulfamethoxazole (TMP/SMX) has been linked to a reactive nitroso intermediate from sulfamethoxazole metabolism, which may be altered in patients with human immunodeficiency virus (HIV) infection. The authors determined the clinical factors that are associated with TMP/SMX hypersensitivity in patients with HIV. In a case control study, 54 controls currently tolerating TMP/SMX prophylaxis were randomly matched by date of hypersensitivity reaction in case patients to 28 patients with a history of a rash consistent with erythema multiforme from TMP/SMX. Demographic data, coadministered medications, laboratory data, and histories of opportunistic infections were extracted on all patients. A highly significant association was observed between the number of opportunistic infections and the occurrence of TMP/SMX hypersensitivity (p < 0.001), despite comparability of CD4 counts between case patients and controls (p > 0.1). A tendency for protection from TMP/SMX hypersensitivity in blacks was also observed (p = 0.066). These observations suggest that the mechanisms by which HIV produces cellular immune dysfunction and alters drug detoxification may be linked.

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