ACETYLATION PHENOTYPE AND CUTANEOUS HYPERSENSITIVITY TO TRIMETHOPRIM-SULFAMETHOXAZOLE IN HIV-INFECTED PATIENTS

Objective: Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX ) is more common in patients with HIV infection. In non-infected patie nts, TMP-SMX hypersensitivity is more common in those with a slow acet ylator phenotype. This study was conducted to determine whether the sl ow acetylation phenotype is associated with an increased risk of hyper sensitivity to TMP-SMX in patients with HIV infection. Methods: Acetyl ation 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 control s. Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (A AMU) and 1-methylxanthine (1-MX), after ingestion of a single 200 mg d ose of caffeine. Results: Of the 28 HIV-infected subjects, 20 (71%) ex pressed 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-S MX hypersensitivity, 15 (94%) had a slow acetylation phenotype, wherea s only five out of 12 (42%) non-hypersensitive subjects had a slow ace tylation phenotype (P < 0.01). Conclusions: A slow acetylation phenoty pe is a risk factor for hypersensitivity to TMP-SMX in HIV-infected su bjects.