University of Bonn, Medicine I, Bonn, Germany.
Expert Opin Investig Drugs. 2011 Apr;20(4):537-48. doi: 10.1517/13543784.2011.562189. Epub 2011 Mar 8.
The recent introduction of integrase inhibitors (INIs) into the HIV treatment armentarium has had a significant impact on HIV treatment. However, at present, raltegravir twice daily is the only licensed INI featuring a lower genetic barrier compared with boosted protease inhibitors. S/GSK1349572 represents a new INI in current development. It is a once-daily, unboosted INI with low pharmacokinetic variability and predictable exposure-response relationship. Phase IIb studies in antiretroviral-naïve patients have demonstrated non-inferiority to efavirenz-based HIV therapy. Phase II studies in INI-experienced patients show partially retained activity in vivo. Overall, the safety profile of S/GSK1349572 in all studies completed has been very favorable.
A Pubmed and Medline search was carried out on all articles on S/GSK1349572 from 2005 to 2010, including recent abstract presentations from major HIV conferences (CROI 2010, WAC2010, EACS2009, HIV10 and ICAAC2010). The reader will become acquainted with the unique properties of this new INI and will understand the current promises and challenges of the data available from S/GSK1349572.
S/GSK1349572 represents a new, unboosted, once-daily INI in development with distinct pharmacokinetics and resistance profile, which has showed promising potency and tolerability in the first clinical studies.
整合酶抑制剂（INIs）的引入对 HIV 治疗产生了重大影响。然而，目前每日两次使用雷替拉韦是唯一具有较低遗传屏障的已获许可的 INI，与强化蛋白酶抑制剂相比。S/GSK1349572 是目前正在开发的一种新型 INI。它是一种每日一次、未强化的 INI，具有较低的药代动力学变异性和可预测的暴露-反应关系。在初治的抗逆转录病毒患者中进行的 IIb 期研究表明，它与基于依非韦伦的 HIV 治疗具有非劣效性。在 INI 经验患者中进行的 II 期研究表明，其在体内仍具有部分活性。总的来说，在所有已完成的研究中，S/GSK1349572 的安全性特征非常有利。
对 2005 年至 2010 年所有关于 S/GSK1349572 的 Pubmed 和 Medline 文章进行了检索，包括来自主要 HIV 会议（CROI 2010、WAC2010、EACS2009、HIV10 和 ICAAC2010）的最新摘要报告。读者将了解这种新型 INI 的独特特性，并了解目前可从 S/GSK1349572 获得的数据所带来的挑战和希望。
S/GSK1349572 是一种新型、未强化、每日一次的 INI，具有独特的药代动力学和耐药性特征，在最初的临床研究中显示出有前途的疗效和耐受性。
