Raltegravir (MK-0518): An integrase inhibitor for the treatment of HIV-1
Raltegravir (MK-0518): An integrase inhibitor for the treatment of HIV-1
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DOI：
10.1358/dot.2007.43.12.1146063
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发表时间：
2007-12-01
期刊：
影响因子：
1.8
通讯作者：
Markowitz, Martin
中科院分区：
文献类型：
--
作者：
Evering, Teresa Hope;Markowitz, Martin
在发达国家，由于获得高效抗逆转录病毒疗法，艾滋病毒/艾滋病的发病率和死亡率大幅下降。然而，对目前可用的抗逆转录病毒药物类别具有抗性的HIV-1菌株的不断出现突出了开发具有新的作用机制的药剂的需要。HIV-1病毒生命周期的成功完成部分取决于由HIV-1整合酶介导的互补DNA的整合，HIV-1整合酶是病毒基因组中编码的三种必需酶之一。整合酶抑制剂已证明能够在整合过程中的链转移步骤中特异性发挥作用，使HIV-1整合酶成为治疗HIV/艾滋病的有效且有吸引力的化疗靶点。在临床试验中，雷特格韦已被证明是一种强效药物，其药代动力学特征支持每日两次给药方案。此外，在未经治疗和有经验的患者中显示了有利的副作用特征，尽管治疗选择有限，但一部分重度治疗患者能够实现雷特格韦联合治疗的病毒学抑制。2007年10月，雷特格韦被美国食品药品监督管理局（FDA）批准用于治疗HIV-1，作为治疗经验丰富的患者的联合抗逆转录病毒疗法的一部分，为HIV-1感染者的管理提供了额外的选择。(c)2007年《科学》杂志。All rights reserved.
In the developed world, access to highly active antiretroviral therapy (HAART) has led to significant reductions in the morbidity and mortality attributed to HIV/AIDS. However, the continual emergence of HIV-1 strains resistant to currently available classes of antiretrovirals highlights the need to develop agents with novel mechanisms of action. Successful completion of the HIV-1 viral life cycle depends in part on the integration of complementary DNA mediated by the enzyme HIV-1 integrase, one of three essential enzymes encoded in the viral genome. The integrase inhibitors have demonstrated the ability to act specifically at the strand transfer step during integration, making HIV-1 integrase a valid and attractive chemotherapeutic target for the treatment of HIV/AIDS. In clinical trials, raltegravir has been shown to be a potent drug with a pharmacokinetic profile that supports a twice-daily dosing schedule. In addition, it has demonstrated a favorable side-effect profile in treatment-naive and -experienced patients and a subset of heavy treatment-experienced patients have been able a achieve virologic suppression with raltegravir as part of combination therapy despite limited treatment options. In October 2007, raltegravir was approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV-1 as part of combination antiretroviral therapy in treatment-experiencied patients-providing an additional option for the management of the HIV-1 infected individual. (c) 2007 Prous Science. All rights reserved.