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Genetic characterization of patients with MHC class I mediated abacavir hypersensitivity reaction

Phillips, E., Rauch, A., Nolan, D., Martin, A., Almeida, C., Knowles, S., Shear, N., Cavassini, M., Harrigan, R., Montaner, J., Keane, N., Laird, R., Lucas, A. and Mallal, S. (2007) Genetic characterization of patients with MHC class I mediated abacavir hypersensitivity reaction. In: 4th International AIDS Conference on HIV Pathogenesis, Treatment and Prevention, 22 - 25 July, Sydney, Australia.

Abstract

Objectives: Abacavir hypersensitivity reaction (ABC HSR) has been closely associated with the MHC Class I allele HLA-B*5701. Patch testing has been useful to identify the true MHC Class I mediated ABC HSR that has been associated with immunological memory and more severe reactions on rechallenge. We examined genetic characteristics of patch test positive (PTP) and patch test negative (PTN) patients who had been clinically labeled with ABC HSR.

Methods: Abacavir PTP and PTN patients were identified from four international clinical sites. Genetic mapping using 57.1 ancestral haplotype(AH) markers at the P5, BAT-1, TNF-238, HSP70-Hom and C4A loci and high resolution HLA typing was carried out on all PTP and PTN patients who had been clinically labeled with ABC HSR.

Results: 25 PTP and 25 PTN patients were identified. 25/25 (100%) of PTP patients were HLA-B*5701 positive versus 2/25 (8%) in the PTN group (p<.0001). 21/23(91.3%) for whom full haplotyping was available carried all 57.1 AH markers examined vs. 0/23 PTN patients (p<.0001). Of 7 PTN patients who had a clinical need for abacavir, all 7 were successfully rechallenged and reestablished on the drug.

Conclusions: A strong correlation exists between ABC patch test positivity and HLA-B*5701 supporting both that patch testing identifies MHC Class I mediated ABC HSR and the robust association between ABC HSR and HLA-B*5701. Recombinant mapping in ABC PTP and PTN patients also suggest close linkage between 57.1 AH markers and ABC HSR and also that HLA-B*5701 is necessary but not sufficient for MHC Class I mediated ABC HSR. Although experience with ABC rechallenge in PTN patients are supportive of the absence of a MHC Class I response in this population, rechallenge should be viewed as a research tool only to be performed in closely monitored settings.

Publication Type: Conference Item
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Conference Website: http://www.iasociety.org/
URI: http://researchrepository.murdoch.edu.au/id/eprint/15729
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