Phillips Elizabeth, Mallal Simon
Institute for Immunology and Infectious Diseases, Murdoch University and Department of Clinical Immunology & Immunogenetics, Royal Perth Hospital, Perth, Western Australia, Australia.
Mol Diagn Ther. 2009;13(1):1-9. doi: 10.1007/BF03256308.
Abacavir hypersensitivity syndrome (AHS) is a potentially life-threatening illness occurring in 4-8% of those initiating the drug. Early studies identified a strong association between the MHC class I allele HLA-B5701 and AHS. These studies suggested that HLA-B5701 holds promise as a screening test to prevent AHS, but concern arose from HLA-B5701-negative cases with a clinical diagnosis of AHS, and particularly from early reports of apparently low sensitivities of HLA-B5701 for AHS in patients of non-White race. However, open screening studies suggested that HLA-B5701 screening can largely eliminate AHS. Furthermore, skin-patch testing was used in later-generation studies to separate those patients with true immunologically mediated AHS from those with false-positive clinical diagnoses. Currently, high-level evidence suggests that HLA-B5701 has a negative predictive value of 100% for patch-test-confirmed AHS, which is generalizable across White and Black populations. Current HIV treatment guidelines have been revised to reflect the recommendation that HLA-B5701 screening be incorporated into routine care for patients who may require abacavir. New laboratory techniques such as PCR and flow cytometric methods, as well as an international quality assurance program, have evolved to ensure the availability of cost-effective screening methods whose consistency and standard can be maintained over time. An elegant body of basic science has evolved, which supports and complements the clinical research in suggesting that AHS is specifically and exquisitely restricted by HLA-B5701 and mediated by CD8+ lymphocytes. Abrogating factors explaining why 45% of those carrying HLA-B*5701 can tolerate abacavir remain to be defined. The research approach applied to AHS has led to a genetic screening test being successfully implemented globally in primary HIV clinical practice. The abacavir 'example' can be applied to other drugs to facilitate the development and operationalization of genetic tests that may be useful to predict and prevent otherwise unpredictable drug reactions.
阿巴卡韦超敏反应综合征（AHS）是一种潜在的危及生命的疾病，在开始使用该药物的患者中发生率为4%-8%。早期研究发现，主要组织相容性复合体（MHC）I类等位基因HLA-B5701与AHS之间存在密切关联。这些研究表明，HLA-B5701有望作为预防AHS的筛查试验，但对于临床诊断为AHS的HLA-B5701阴性病例，尤其是早期关于非白种人患者中HLA-B5701对AHS的敏感性明显较低的报道，引发了人们的担忧。然而，开放性筛查研究表明，HLA-B5701筛查可在很大程度上消除AHS。此外，在后续研究中采用皮肤斑贴试验，将真正由免疫介导的AHS患者与临床诊断为假阳性的患者区分开来。目前，高级别证据表明，对于斑贴试验确诊的AHS，HLA-B5701的阴性预测值为100%，这在白种人和黑种人群体中均适用。当前的艾滋病病毒治疗指南已修订，以反映将HLA-B5701筛查纳入可能需要阿巴卡韦治疗的患者常规护理的建议。诸如聚合酶链反应（PCR）和流式细胞术方法等新的实验室技术，以及一项国际质量保证计划已经发展起来，以确保能够获得具有成本效益的筛查方法，其一致性和标准能够长期维持。一系列精妙的基础科学研究已经展开，支持并补充了临床研究，表明AHS受到HLA-B5701的特异性和精确限制，并由CD8+淋巴细胞介导。解释为何45%携带HLA-B*5701的人能够耐受阿巴卡韦的消除因素仍有待确定。应用于AHS的研究方法已促使一项基因筛查试验在全球原发性艾滋病病毒临床实践中成功实施。阿巴卡韦的“范例”可应用于其他药物，以促进基因检测的开发和应用，这些检测可能有助于预测和预防其他不可预测的药物反应。
