New approaches for quantitating the inhibition of HIV-1 replication by antiviral drugs in vitro and in vivo.
New approaches for quantitating the inhibition of HIV-1 replication by antiviral drugs in vitro and in vivo.
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DOI：
10.1097/qco.0b013e328332c54d
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发表时间：
2009-12
影响因子：
3.9
通讯作者：
Siliciano RF
中科院分区：
文献类型：
--
作者：
McMahon MA;Shen L;Siliciano RF
随着高效抗逆转录病毒疗法（HAART）的出现，HIV-1感染已成为一种可控制的终身疾病。开发最佳治疗方案需要了解如何最好地测量体外抗HIV活性以及体外产生的药物剂量反应曲线如何与体内疗效相关。最近的几项研究表明，传统的多轮感染性试验在低水平和高水平的抑制下都不如单循环试验。多轮感染性检测可能无法检测到细微但具有临床意义的抗HIV活性。单轮感染性试验促进了B型肝炎药物恩替卡韦和单纯疱疹药物阿昔洛韦抗艾滋病毒活性的发现。最近使用单轮感染性试验的研究表明，以前被忽视的参数，剂量反应曲线斜率，是抗病毒活性的一个非常重要的决定因素。一些抗逆转录病毒药物具有陡峭的斜率，从而导致异常水平的抗病毒活性。瞬时抑制电位（IIP），在临床药物浓度下的单轮试验中感染性的对数减少，已被提出作为一种新的指标，用于比较抗病毒活性。在抗病毒活性的体外测量中，单轮感染测定具有测量药物的瞬时抑制的优点。重新评估已批准的HIV-1药物的抗病毒活性表明，斜率参数是药物活性的重要因素。通过使用单轮感染性测定来确定IIP可以提供重要的见解，其可以预测抗HIV-1药物的体内功效。
With highly active anti-retroviral therapy (HAART), HIV-1 infection has become a manageable lifelong disease. Developing optimal treatment regimens requires understanding how to best measure anti-HIV activity in vitro and how drug dose response curves generated in vitro correlate with in vivo efficacy. Several recent studies have indicated that conventional multi-round infectivity assays are inferior to single cycle assays at both low and high levels of inhibition. Multi-round infectivity assays can fail to detect subtle but clinically significant anti-HIV activity. The discoveries of the anti-HIV activity of the hepatitis B drug entecavir and the herpes simplex drug acyclovir were facilitated by single round infectivity assays. Recent studies using a single round infectivity assay have shown that a previously neglected parameter, the dose response curve slope, is an extremely important determinant of antiviral activity. Some antiretroviral drugs have steep slopes that result in extraordinary levels of antiviral activity. The instantaneous inhibitory potential (IIP), the log reduction in infectivity in a single round assay at clinical drug concentrations, has been proposed as a novel index for comparing antiviral activity. Among in vitro measures of antiviral activity, single round infection assays have the advantage of measure instantaneous inhibition by a drug. Re-evaluating the antiviral activity of approved HIV-1 drugs has shown that the slope parameter is an important factor in drug activity. Determining the IIP by using a single round infectivity assay may provide important insights that can predict the in vivo efficacy of anti-HIV-1 drugs.