84-P: HEAT SHOCK PROTEIN-70 Hom M493T GENOTYPING INCREASES THE PREDICTIVE POTENTIAL OF HLA-B∗5701 AS A PHARMACOGENETIC TEST FOR ABACAVIR HYPERSENSITIVITY

Abstract

Abacavir is a reverse transcriptase inhibitor used to treat patients with HIV-1. Approximately 5-10% of patients treated with Abacavir develop a potentially fatal Abacavir hypersensitivity syndrome (AHS). In a cohort of 488 HIV-1 positive patients, our research group has earlier shown patients carrying HLA B∗57:01 allele are at high risk of developing AHS. However, among HLA-B∗57:01 positive patients, who were treated with Abacavir, 10% were tolerant to Abacavir while the remaining 90% developed AHS. This suggests that other immunogenetic factors in addition to the carriage of HLA-B∗57:01 may also be involved in the pathogenesis of AHS. One such immunogenetic factor is Hsp-70Hom chaperone involved in presentation of Abacavir hapten to T cells. In the present study, we aim to determine if genotyping HIV-1 positive patients for Hsp-70 Hom M 493 T and HLA-B∗5701 will be better predictive of AHS than genotyping HLA-B∗57:01 alone. All HLA-B∗57:01 positive patients (n=20) from the same cohort of 488 HIV-1 patients were genotyped for Hsp-70 Hom M 493 T (defined T/C substitution at 9564 position). Genotyping was achieved by sequencing codon 493 of the Hsp-70 Hom gene. Both HLA-B∗57:01 positive patients who were tolerant of Abacavir were not found to be carrying the ancestral Hsp-70 Hom T allele (genotyped as C/C at 9564C > T). However, all other HLA-B∗57:01 positive individuals who developed AHS had a C/T genotype at 9564C > T. A 100% sensitivity and specificity was observed when a combined pharmacogenetic test (HLA_B∗57:01 and Hsp-70 Hom M 493 T genotyping) was used for prediction of AHS. Absence of the T allele on the Hsp-70 Hom M 493 T gene protects those who are HLA-B∗57:01 positive from developing Abacavir hypersensitivity syndrome. Genotyping Hsp-70 Hom M 493 T together with HLA-B∗57:01 will significantly increase the predictive potential of the pharmacogenetic testing for ABH.