Mechanisms of drug hypersensitivity in HIV-infected patients: the role of the immune system

Abstract

Drug hypersensitivity is a major problem in HIV medicine. These reactions limit the choice of antiretrovirals that can be used in a patient and, at times, can lead to failure to administer an adequate regimen. Hypersensitivity reactions occur in a minority of patients, but represent a high cost both to the patient and to health services. Our current understanding of these reactions is based on the hapten and the danger hypotheses, which state that a drug signal by itself is insufficient to induce an immune response but must be accompanied by co-stimulatory or danger signals. Furthermore, individual susceptibility to a hypersensitivity reaction may be determined by genetic factors. In this review, we explore our understanding of the immunological mechanisms of hypersensitivity to drugs used in HIV-positive patients, by using sulphamethoxazole and abacavir as paradigms. A deeper understanding of the mechanism(s) of these reactions will help us in their prevention, diagnosis and treatment.