Phillips Elizabeth J, Mallal Simon A
Institute for Immunology & Infectious Diseases, Murdoch University, Department of Clinical Immunology & Immunogenetics, 2nd Floor North Block, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000.
Royal Perth Hospital, Perth, Western Australia.
Per Med. 2009 Jul;6(4):393-408. doi: 10.2217/pme.09.12.
The concept of personalizing antiretroviral therapy is not novel, since the complexity of the HIV patient and their therapy has always demanded consideration of the patient's 'pharmacoecology', taking into account factors such as adherence, drug-drug and food-drug interactions, underlying disease and host states, such as organ dysfunction and pregnancy. Recent advances in science have taken this one step further with the technology now available to use both a candidate and whole-genome approach to explore the genetics of host-virus interactions, as well as the pharmacogenetics of the toxicity and efficacy of antiretroviral therapy. The genetics of host-virus interactions have improved our understanding of the pathogenesis of HIV which will aid in the research and development of an HIV vaccine. Most published HIV pharmacogenetic studies have utilized a candidate gene approach. Although these types of studies have provided insight into the pathogenesis and pharmacogenetics of drug disposition, drug interactions, drug efficacy and toxicity and host-virus interactions, very few will lend themselves to a widespread clinical application. The application of HLA-B*5701 screening to prevent abacavir hypersensitivity acts as an important example of the successful widespread implementation of a pharmacogenetic test into the clinic and defines the key steps necessary for the clinical application of pharmacogenetic tests in general.
个性化抗逆转录病毒疗法的概念并不新颖，因为艾滋病患者及其治疗的复杂性一直要求考虑患者的“药物生态学”，要考虑诸如依从性、药物相互作用和食物-药物相互作用、基础疾病和宿主状态（如器官功能障碍和妊娠）等因素。随着现有技术可采用候选基因和全基因组方法来探索宿主-病毒相互作用的遗传学以及抗逆转录病毒疗法的毒性和疗效的药物遗传学，科学上的最新进展又向前迈进了一步。宿主-病毒相互作用的遗传学增进了我们对艾滋病发病机制的理解，这将有助于艾滋病疫苗的研发。大多数已发表的艾滋病药物遗传学研究都采用了候选基因方法。尽管这类研究为药物处置、药物相互作用、药物疗效和毒性以及宿主-病毒相互作用的发病机制和药物遗传学提供了见解，但很少有研究能广泛应用于临床。HLA-B*5701筛查用于预防阿巴卡韦超敏反应，是药物遗传学检测成功广泛应用于临床的一个重要例子，并总体上界定了药物遗传学检测临床应用所需的关键步骤。
