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Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity.

Abstract：

:Adverse reactions to sulfonamides occur at a higher frequency in patients infected with the human immunodeficiency virus (HIV) than noninfected patients. Some studies have suggested that patients with the slow acetylator phenotype are predisposed to these reactions, whereas other studies suggest that the slow acetylator genotype is not a predisposing factor. To rationalize these seemingly contradictory observations, the authors determined the N-acetyltransferase 2 (NAT2) genotype and phenotype in patients with and without a history of hypersensitivity reactions to sulfonamides. HIV-infected patients with a history of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were enrolled, along with a group of AIDS patients with no history of hypersensitivity (delayed or immediate). NAT2 phenotype was determined in both groups using dapsone, while the genotype was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of 14 patients (57%) without such a history exhibited this same phenotype (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a history exhibited this genotype (ns). There were more instances of discordance between deduced and actual phenotype in the nonhypersensitive patients (n = 4) than in the hypersensitive patients (n = 1). The reported higher frequency of the slow acetylator phenotype among patients with a history of hypersensitivity to sulfonamides does not appear to be explained by metabolic changes that would cause discordance between acetylator genotype and phenotype.

journal_name

J Clin Pharmacol

journal_title

Journal of clinical pharmacology

authors

O'Neil WM,MacArthur RD,Farrough MJ,Doll MA,Fretland AJ,Hein DW,Crane LR,Svensson CK

doi

10.1177/00970002042006004

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

613-9

issue

eissn

0091-2700

issn

1552-4604

journal_volume

pub_type

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Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity.