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Abacavir is a commonly prescribed HIV drug belonging to the nucleoside reverse transcriptase inhibitor (NRTI) class. The major treatment-limiting side effect associated with its use is an early onset multi-system drug hypersensitivity re-action typically including some combination of rash, fever and gastrointestinal symptoms, occurring within 6 weeks of initiating treatment in approximately 5-8% of abacavir recipients. Susceptibility to this drug hypersensitivity syn-drome is strongly predicted by the presence of a specific human leukocyte antigen (HLA) allele -HLA-B * 5701 -which represents the dominant risk factor for abacavir hypersen-sitivity among Caucasian and Hispanic populations. The frequency distribution of this genetic marker in different populations is likely to provide a rational basis for racially-defined differences in susceptibility, while the critical role of HLA-B * 5701 in directing CD8+ T-cell-dependent, HLA-restricted immune responses provides a key role for this genetic variant in the pathogenesis of abacavir-specific immune responses. In this chapter, we review the implications of this genetic association for clinical practice as well as current knowledge of its immunological basis.
|Publication Type:||Book Chapter|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||S. Karger AG|
|Copyright:||© 2007 S. Karger AG|
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