Acetylation phenotype and cutaneous hypersensitivity to trimethoprim-sulphamethoxazole in HIV-infected patients

Abstract

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) is more common in patients with HIV infection. In non-infected patients, TMP-SMX hypersensitivity is more common in those with a slow acetylator phenotype. This study was conducted to determine whether the slow acetylation phenotype is associated with an increased risk of hypersensitivity to TMP-SMX in patients with HIV infection. Acetylation phenotype was determined in 28 HIV-infected subjects, of whom 16 had prior TMP-SMX hypersensitivity and 12 had received long-term TMP-SMX therapy without hypersensitivity, as well as in 29 healthy controls. Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (AAMU) and 1-methylxanthine (1-MX), after ingestion of a single 200 mg dose of caffeine. Of the 28 HIV-infected subjects, 20 (71%) expressed a slow acetylation phenotype and eight (29%) a fast phenotype. By comparison, of the 29 healthy controls, 15 (52%) expressed a slow phenotype (P = 0.11). Of the 16 HIV-infected subjects with prior TMP-SMX hypersensitivity, 15 (94%) had a slow acetylation phenotype, whereas only five out of 12 (42%) non-hypersensitive subjects had a slow acetylation phenotype (P < 0.01). A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects.