[Intolerance to sulfonamides in HIV infected subjects. Toxic and allergic origin]

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types 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 represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.