HLA-B*5701 Taqman assay for abacavir sensitivity: Application to PREDICT-1 trial
Bugawan, T., Isoda, W., Mallal, S., Thorborn, D. and Erlich, H. (2008) HLA-B*5701 Taqman assay for abacavir sensitivity: Application to PREDICT-1 trial. In: 34th Annual Meeting of the American Society for Histocompatibility and Immunogenetics (ASHI) 2008, 27 - 31 October 2008, Toronto, Canada.
Aim: Around 5% of HIV infected patients treated with the HIV drug abacavir experience an allergic hypersensitive response within 6 weeks. Genetic association studies have shown that the HLA-B*5701 allele is highly associated with abacavir hypersensitivity (Mallal et al 2002). and studies of in vitro T cell responses to abacavir pulsed APC indicate that the B*5701 allele is a causal determinant of allergic hypersensitivity (Chessman et al 2007). Our aim was to develop a real-time PCR method of detecting the B*5701 allele on the same automated platform (Cobas AmpliPrep/Cobas TaqMan;CAP/CTM) currently used for determining HIV viral load.
Methods: The B*5701 CTM is a single tube, 2 channel research assay using 2 pairs of primers and Hex- and Fam-labeled Taqman probes. A Hex labeled control probe binds to the exon 2 of all HLA-B alleles. The exon 3 primers and the Fam labeled probe are B*5701 specific.
Results: This assay was used to determine the B*5701 status of 1956 DNA samples from the PREDICT-1 study (Mallal et al 2008). This study demonstrated the clinical utility of B*5701 screening prior to abacavir treatment. HLA-B*5701 status was independently determined by using SSOP followed by SBT for HLA-B57 positive samples (LabCorp) as well as SBT single step full allelic typing (Perth). The Roche CTM HLA-B*5701 results are fully concordant with the sequencing results. Currently, this research assay can be run on whole blood in the same integrated CAP/CTM platform used for measuring HIV viral load.
Conclusions: The HLA-B*5701 CAP/CTM assay is a valuable research screening test for determining HLA-B*5701 status in abacavir-naï ve HIV patients.
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|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
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