INTOLERANCE TO SULFONAMIDES IN HIV-INFECT ED SUBJECTS - TOXIC AND ALLERGIC ORIGINS

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 t ypes of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and repre sent the vast majority of allergic manifestations in HIV-infected subj ects. Clinically, these reactions resemble serum sickness, but all phy siopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway whi ch is genetically determined and saturable, and the cytochrome P450 pa thway which produces toxic hydroxylamine metabolites <<detoxified>> by glutathion. In HIV-infected subjects detoxication is thought to be in complete due to an acquired deficiency of glutathion and probably incr eased in the presence of a slow acetylation profile.