Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GL, UK.
Br J Clin Pharmacol. 2011 May;71(5):659-71. doi: 10.1111/j.1365-2125.2010.03784.x.
Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions.
许多用于治疗 HIV 疾病(包括相关机会性感染)的药物会引起药物过敏反应,其严重程度、临床表现和频率各不相同。这些反应不仅见于旧的化合物,也见于新的、最近引入的药物。大多数情况下,发病机制尚不清楚,但越来越多的证据表明,许多反应是通过主要组织相容性复合体(MHC)的免疫和遗传因素的组合介导的。一些药物的过敏反应发生具有遗传易感性,这在阿巴卡韦过敏中表现得尤为明显,它与 I 类 MHC 等位基因 HLA-B*5701 强烈相关。在开具阿巴卡韦之前进行检测已被证明具有临床实用性,已导致药物标签发生变化,现在被临床指南推荐,并且在大多数西方国家都得到了实践。然而,对于大多数其他药物,目前还没有很好的预防方法,需要进行临床监测,并适当使用(通常是支持性和对症性)治疗。需要在这一领域进行进一步的研究,以增加我们对机制的了解,这可能通过开发预测性遗传生物标志物或通过指导设计不太可能引起这些类型不良反应的药物来实现更好的预防策略。