aVanderbilt University School of Medicine, Nashville, Tennessee, USA bKantonsspital Baselland, University of Basel, Bruderholz, Switzerland.
Curr Opin HIV AIDS. 2015 Mar;10(2):116-22. doi: 10.1097/COH.0000000000000134.
To summarize current knowledge and provide perspective on relationships between human genetic variants, antiretroviral medications, and aging-related complications of HIV-1 infection.
Human genetic variants have been convincingly associated with interindividual variability in antiretroviral toxicities, drug disposition, and aging-associated complications in HIV-1 infection. Screening for HLA-B5701 to avoid abacavir hypersensitivity reactions has become a routine part of clinical care, and has markedly improved drug safety. There are well established pharmacogenetic associations with other agents (efavirenz, nevirapine, atazanavir, dolutegravir, and others), but this knowledge has yet to have substantial impact on HIV-1 clinical care. As metabolic complications including diabetes mellitus, dyslipidemia, osteoporosis, and cardiovascular disease are becoming an increasing concern among individuals who are aging with well controlled HIV-1 infection, human genetic variants that predispose to these complications also become more relevant in this population.
Pharmacogenetic knowledge has already had considerable impact on antiretroviral prescribing. With continued advances in the field of human genomics, the impact of pharmacogenomics on HIV-1 clinical care and research is likely to continue to grow in importance and scope.
总结目前关于人类遗传变异体、抗逆转录病毒药物与 HIV-1 感染相关的衰老并发症之间关系的知识，并提供新视角。
人类遗传变异体与抗逆转录病毒药物毒性、药物处置以及 HIV-1 感染相关的与衰老相关的并发症的个体间变异性之间存在令人信服的关联。筛查 HLA-B5701 以避免阿巴卡韦超敏反应已成为临床护理的常规部分，大大提高了药物安全性。还有与其他药物（依非韦伦、奈韦拉平、阿扎那韦、多替拉韦等）的明确的药物遗传学关联，但这些知识尚未对 HIV-1 临床护理产生实质性影响。随着代谢并发症（包括糖尿病、血脂异常、骨质疏松症和心血管疾病）在 HIV-1 感染得到良好控制的人群中变得越来越令人担忧，易患这些并发症的人类遗传变异体在该人群中也变得更加相关。
药物遗传学知识已经对抗逆转录病毒药物的处方产生了相当大的影响。随着人类基因组学领域的持续进步，药物遗传学对 HIV-1 临床护理和研究的影响可能会继续变得更加重要和广泛。
