Mechanisms of drug hypersensitivity in HIV-infected patients: the role of the immune system.
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.
Vilar
F Javier
FJ
Department of Infectious Diseases, North Manchester General Hospital, Delaunays Road, Crumpsall, Manchester M8 5RB, UK. Javier.Vilar@mail.nmanhc-tr.nwest.nhs.uk
Naisbitt
Dean J
DJ
Park
B Kevin
BK
Pirmohamed
Munir
M
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000627:therapeutic use; D000099227:Abacavir
D000900:Anti-Bacterial Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000099227:Abacavir