Mahungu T W, Johnson M A, Owen A, Back D J
Department of HIV Medicine, Royal Free NHS Trust, Pond Street, London NW3 2QG.
Int J STD AIDS. 2009 Mar;20(3):145-51. doi: 10.1258/ijsa.2008.008369.
The use of highly active antiretroviral therapy in the treatment of HIV infection has resulted in significant reductions in mortality and morbidity worldwide. However, there is considerable interindividual variability in patient outcomes in terms of drug disposition, drug efficacy and adverse events. The basis of these differences is multifactorial, but host genetics are believed to play a significant part. To date, most attempts to explain this variability have focused on isolated single nucleotide polymorphisms. The most exciting development to date is the discovery of human leukocyte antigen subtype B5701 (HLA B5701) as a strong predictor of the abacavir hypersensitivity reaction. There is a gradual move away from single candidate gene analyses towards a high throughput whole genome approach. These studies must be performed on well characterized cohorts and reported associations must be validated in independent, ethnically diverse populations.
在全球范围内,使用高效抗逆转录病毒疗法治疗HIV感染已使死亡率和发病率显著降低。然而,在药物处置、药物疗效和不良事件方面,患者的治疗结果存在相当大的个体差异。这些差异的原因是多方面的,但宿主遗传学被认为起着重要作用。迄今为止,大多数解释这种变异性的尝试都集中在孤立的单核苷酸多态性上。迄今为止最令人兴奋的进展是发现人类白细胞抗原B5701亚型(HLA B5701)是阿巴卡韦超敏反应的强预测指标。目前正逐渐从单一候选基因分析转向高通量全基因组方法。这些研究必须在特征明确的队列中进行,并且所报告的关联必须在独立的、种族多样的人群中得到验证。