Flexner Charles W
Johns Hopkins University, Baltimore, MD, USA.
Top HIV Med. 2003 Mar-Apr;11(2):40-4.
Developing better antiretroviral drugs, individualizing therapy through patient genetic profiling, and maintaining effective drug concentrations with therapeutic drug monitoring (TDM) represent 3 current areas of interest in the field of HIV pharmacology. This article first examines antiretroviral drug binding to plasma proteins, a factor that affects the amount of free drug available to enter cells. Protein binding influences drug development, raising questions about whether the drug levels required for appropriate therapeutic effect can be achieved at tolerable doses. Second, individualized antiretroviral therapy has generated considerable interest, but much work remains in the area of pharmacogenomics before this strategy finds a place in clinical practice. Finally, studies are mixed on the benefits of TDM; although such monitoring may be appropriate in some settings, such as pregnancy and pediatrics, data are currently lacking to support its routine use in HIV care. Although data on these pharmacologic strategies do not currently support their widespread clinical application, ongoing research of such strategies offers hope for future improvement of the efficacy of antiretroviral therapy. This article summarizes a presentation given by Charles W. Flexner, MD, at the November 2002 International AIDS Society-USA course in San Diego.
研发更有效的抗逆转录病毒药物、通过患者基因谱分析实现个体化治疗以及利用治疗药物监测（TDM）维持有效的药物浓度，是目前HIV药理学领域的三个研究热点。本文首先探讨抗逆转录病毒药物与血浆蛋白的结合情况，这是影响可进入细胞的游离药物量的一个因素。蛋白结合会影响药物研发，引发了关于能否在可耐受剂量下达到适当治疗效果所需药物水平的疑问。其次，个体化抗逆转录病毒治疗引起了广泛关注，但在该策略在临床实践中得到应用之前，药物基因组学领域仍有许多工作要做。最后，关于TDM的益处的研究结果不一；尽管在某些情况下，如妊娠和儿科，这种监测可能是合适的，但目前缺乏支持其在HIV治疗中常规使用的数据。虽然目前关于这些药理学策略的数据不支持它们在临床上的广泛应用，但对这些策略的持续研究为未来提高抗逆转录病毒治疗的疗效带来了希望。本文总结了医学博士查尔斯·W·弗莱克斯纳在2002年11月于圣地亚哥举行的美国国际艾滋病学会课程上的一次演讲。
