抗反转录病毒药物不良反应的药物遗传学。
Pharmacogenetics of adverse effects due to antiretroviral drugs.
机构信息
Sección de Enfermedades Infecciosas y VIH/SIDA, Departamento de Medicina Interna, Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
出版信息
AIDS Rev. 2010 Jan-Mar;12(1):15-30.
The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and chronic toxicities associated with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy, liver damage, and the appearance of body fat redistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicities are family- or even drug-specific. Since not all patients that take a particular antiretroviral medication develop the adverse effect that has been attributed to that drug, it has therefore been postulated that there must be a genetically conditioned individual predisposition to developing the adverse effect. Pharmacogenetics is the science that studies interindividual variations in the response to and toxicity of pharmaceuticals due to variations in the genetic composition of individuals - in other words, how a person's genetic make-up influences the favorable or adverse effects of a certain treatment. Sufficient advances have been made in this discipline to allow this fertile field of research to move out of the basic science laboratory and into clinical applications. The present article reviews the investigations that have been published regarding the association between genetic determinants of persons infected with HIV and clinical toxicity resulting from different antiretroviral drugs. Special emphasis is devoted to the studies that have resulted in clinical applications such as that of the pre-screening of HLA B*5701 for avoiding abacavir-related hypersensitivity syndrome.
高效抗逆转录病毒疗法的出现显著提高了感染 HIV 患者的生存率和生活质量。然而,目前仍然没有治愈 HIV 的方法,接受治疗的患者必须终生接受治疗。抗逆转录病毒药物的使用与多种毒性有关,这些毒性限制了它们的成功。这些药物引起的一些急性和慢性毒性包括过敏反应、神经毒性、肾病、肝损伤以及身体脂肪重新分布综合征和随之而来的不同代谢改变。其中一些毒性具有家族性甚至是药物特异性。由于并非所有服用特定抗逆转录病毒药物的患者都会出现归因于该药物的不良反应,因此有人假设,个体对不良反应的易感性一定存在遗传决定因素。药物遗传学是研究由于个体遗传组成的差异而导致对药物的反应和毒性存在个体间差异的科学——换句话说,一个人的基因构成如何影响特定治疗的有利或不利影响。这一学科已经取得了足够的进展,可以将这一富有成效的研究领域从基础科学实验室推向临床应用。本文综述了已发表的关于 HIV 感染者的遗传决定因素与不同抗逆转录病毒药物引起的临床毒性之间关联的研究。特别强调了那些已经产生临床应用的研究,例如 HLA B*5701 的预筛选以避免与阿巴卡韦相关的过敏反应综合征。