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Drug hypersensitivity has been reported to occur 100 times more commonly in those living with HIV. In the first decade of HIV treatment, this mainly involved drugs used to treat HIV-related infections but now primarily includes drugs used to treat HIV. This review focuses on the current knowledge of the epidemiology, pathophysiology and clinical features of drug hypersensitivity reactions of drugs used in the management of the HIV-infected patient.Our understanding of the immunogenetics and host predisposition to drug hypersensitivity has been advanced considerably by the antiretroviral drugs abacavir and nevirapine. The association of abacavir hypersensitivity reaction with HLA-B*5701 has been particularly important and provides a basis for genetic screening in the clinic setting.The increased predisposition of drug hypersensitivity disease in HIV will continue to provide a fertile ground for study of the diverse and complex processes that drive its pathophysiology. Our knowledge of drug hypersensitivity will also increase as the expanding armentarium of antiretroviral therapy is applied to more diverse populations in the developing world. The potential for widespread implementation of HLA-B*5701 screening for abacavir hypersensitivity will set an important precedent for bringing individualized medicine to the clinic and the use of genetic testing to improve drug safety.