Morse Gene D, Catanzaro Linda M, Acosta Edward P
Department of Pharmacy Practice, University at Buffalo, State University of New York, Amherst 14260, USA.
Lancet Infect Dis. 2006 Apr;6(4):215-25. doi: 10.1016/S1473-3099(06)70436-4.
The introduction of HIV-1 protease inhibitors and non-nucleoside reverse transcriptase inhibitors in 1996 began an era described as that of highly active antiretroviral therapy. In addition, the more recent development and availability of HIV-1 genotypic and phenotypic resistance tests and advances in pharmacological assays that support therapeutic drug monitoring (TDM) have created tools that may help clinicians to provide more individualised treatment with HIV-1 protease inhibitors. All current treatment guidelines provide fixed doses of protease inhibitors with vague recommendations for the use of TDM in selected clinical situations. In patients with resistance to protease inhibitors, the combined use of resistance tests with TDM provide a mechanism for individualising the clinical pharmacodynamics of protease inhibitors. Current therapeutic approaches seek to include the monitoring of protease-inhibitor concentrations as part of a TDM programme with phenotypic assays to calculate an inhibitory quotient, virtual inhibitory quotient, or normalised inhibitory quotient, whereas genotypic tests are used with TDM to calculate a genotypic inhibitory quotient. Current investigation is focused on examining the predictive value of this approach for clinical monitoring.
1996年引入的HIV-1蛋白酶抑制剂和非核苷类逆转录酶抑制剂开启了一个被称为高效抗逆转录病毒治疗的时代。此外，HIV-1基因型和表型耐药性检测的最新发展及可用性，以及支持治疗药物监测（TDM）的药理学检测方法的进步，创造了一些工具，可能有助于临床医生使用HIV-1蛋白酶抑制剂提供更个体化的治疗。目前所有的治疗指南都提供了蛋白酶抑制剂的固定剂量，并对在特定临床情况下使用TDM给出了模糊的建议。在对蛋白酶抑制剂耐药的患者中，耐药性检测与TDM的联合使用为蛋白酶抑制剂的临床药效学个体化提供了一种机制。当前的治疗方法试图将蛋白酶抑制剂浓度监测纳入TDM计划的一部分，通过表型检测来计算抑制商、虚拟抑制商或标准化抑制商，而基因型检测则与TDM一起用于计算基因型抑制商。目前的研究重点是检验这种方法对临床监测的预测价值。
