REACTIONS TO TRIMETHOPRIM-SULFAMETHOXAZOLE IN AIDS

获得性免疫缺陷综合症（艾滋病）患者

Individuals with acquired immunodeficiency syndrome (AIDS) frequently suffer from opportunistic viral, microbial, fungal, and protozoan infections. The treatment of choice for opportunistic protozoan infections commonly includes sulfonamide drugs, and especially the combination of sulfamethoxazole and trimethoprim. AIDS patients, despite their severely depressed Immune function, frequently experience adverse reactions to sulfamethoxazole- trimethoprim, which are highly suggestive of hypersensitivity; symptoms include worsening of neutropenia and thrombocytopenia, diffuse skin rash, persistent fever, and occasionally shock. This study will evaluate whether specific humoral and cellular hyperreactivity to sulfamethoxazole-trimethoprim and related anti-protozoan drugs are major causes of these adverse reactions. Studies will include evaluation of Type I, II, and III hypersensitivity (measurement of class specific antibodies to several sulfonamides; pyrimidines; the sulfone, dapsone; and combinations of these drugs) and of Type IV cell mediated hypersensitivity (the ability of these drugs and their metabolites to induce lymphocyte proliferation). Immunologic and non- immunologic basophil degranulation by sulfonamide-trimethoprim drugs will also be evaluated. Findings from these studies will not only provide important information regarding the nature of adverse reactions to drugs essential to the prophylaxis and treatment of opportunistic infections, such as pneumocystis carinii and toxoplasmosis in AIDS patients, but also for treatment of many protozoan infections, including malaria, in immunocompetent normals. In addition, the results will provide a better understanding of altered immune responses in AIDS patients.