Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Pharmacogenomics. 2011 Apr;12(4):567-76. doi: 10.2217/pgs.10.208.
International HIV treatment guidelines recommend HLA-B57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B57:01 detection has been developed in the present study.
MATERIALS & METHODS: Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR.
A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with κ = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples.
We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping. Original submitted 26 October 2010; Revision submitted 13 December 2010.
国际 HIV 治疗指南建议在使用阿巴卡韦前进行 HLA-B57:01 基因分型，以降低阿巴卡韦过敏反应的发生率，这种反应是导致早期治疗中断的主要原因。本研究中开发了一种快速、敏感和特异的 HLA-B57:01 检测方法。
设计了 2 套序列特异性引物，并通过实时 PCR 快速扩增。
在一项单盲研究中分析了 108 例样本，其中 41 例被鉴定为阳性。与由葛兰素史克公司资助的 EPI109367 临床试验中使用的验证方法（包括低分辨率序列特异性寡核苷酸 PCR 及对 HLA-B*57 阳性样本进行的高分辨率序列特异性寡核苷酸 PCR）完全一致，κ=1（标准误差=0.0962，p<0.0001）。
我们详细描述了一种新的 HLA-B*57:01 筛选检测方法，已经参与病毒载量和病毒基因分型检测的实验室可以很容易地实施该方法。原始提交日期为 2010 年 10 月 26 日；修订后提交日期为 2010 年 12 月 13 日。
