Studies on abacavir-induced hypersensitivity reaction:a successful example of translation of pharmacogenetics to personalized medicine  

作　　者：GUO YongLi SHI LeMing HONG HuiXiao SU ZhenQiang FUSCOE James NING BaiTang 

机构地区：[1]Division of Systems Biology,National Center for Toxicological Research,the US Food and Drug Administration [2]Division of Bioinformatics and Biostatistics,National Center for Toxicological Research,the US Food and Drug Administration

出　　处：《Science China(Life Sciences)》2013年第2期119-124,共6页中国科学（生命科学英文版）

摘　　要：Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus （HIV） infected patients. Its main side effect is hypersensitivity reaction （HSR）. The incidence of the HSR is associated with ethnicity among patients exposed to abacavir, and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen （HLA）-B＊57：01-carrying patients. Immunological studies indicated that abacavir interacts specifically with HLA-B＊57：01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire, leading to a systemic autoimmune reaction. HLA-B＊57：01 screening, com- bined with patch testing, had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B＊57：01 prevalence in the population. Therefore, the US Food and Drug Administration （FDA） and international HIV treatment guidelines recommend a routine HLA-B＊57：01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR. The studies of abacavir-induced HSR and the implementation of the HLA-B＊57：01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.

关 键 词：personalized medicine PHARMACOGENETICS drug safety ABACAVIR hypersensitivity reaction （HSR） HLA-B＊57：01 HLA-B＊57-01 screening 

分 类 号：R96[医药卫生—药理学]