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


METHODS
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.


RESULTS
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).


CONCLUSIONS
A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects.
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
A
A
Carr
A S
AS
Gross
J M
JM
Hoskins
R
R
Penny
D A
DA
Cooper
D000107:Acetylation; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism
D002110:Caffeine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001191:Arylamine N-Acetyltransferase