Comparative study of the persistence of anti-HIV activity of deoxynucleoside HIV reverse transcriptase inhibitors after removal from culture.
Comparative study of the persistence of anti-HIV activity of deoxynucleoside HIV reverse transcriptase inhibitors after removal from culture.
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DOI：
10.1186/1742-6405-6-5
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发表时间：
2009-04-22
影响因子：
2.2
通讯作者：
Cheng YC
中科院分区：
文献类型：
--
作者：
Paintsil E;Grill SP;Dutschman GE;Cheng YC
大多数药物效力的体外试验可能无法充分预测体内性能。评估脱氧核苷类似物的抗病毒活性的持久性的方法对于设计剂量、组合方案和评估治疗依从性将是重要的，脱氧核苷类似物需要细胞内活化为可以在细胞中持久存在的活性代谢物。使用HIV-IIIB/TZM-bl指示细胞培养系统，我们评估了抑制剂保护细胞免受感染和从培养物中去除抑制剂后延迟病毒反弹的能力。对HIV感染细胞的保护作用顺序为：4 '-Ed 4 T> LFD 4C> DDI > D4 T> 3 TC> AZT > FTC > NVP。延迟病毒反弹的EC 50增加倍数为DDI <4 '-Ed 4 T <LFD 4C < FTC <D4 T <3 TC < NVP < AZT. The ranking of persistence of anti-HIV activity of the inhibitors based on the two-component assay was DDI >4'-Ed 4 T> LFD 4C> FTC = D4 T> 3 TC> NVP > AZT。持久性排序来自基于单个病毒复制周期和多个时间点累积抑制的测定的测定。因此，是抑制剂药效学特性的更好指标。抗HIV活性测定的持续性可以补充体外效力测定，以更好地预测核苷类似物的体内性能。
Most in vitro assays of drug potency may not adequately predict the performance in vivo. Methods to assess the persistence of antiviral activity of deoxynucleoside analogs, which require intracellular activation to the active metabolites that can persist in cells, will be important for designing dosages, combination regimens, and assessing treatment compliance. Using an HIV-IIIB/TZM-bl indicator cell culture system, we assessed the ability of an inhibitor to protect cells from infection and to delay viral rebound after removal of inhibitor from culture. The order of protection of cells from HIV-infection was 4'-Ed4T > LFD4C > DDI > D4T > 3TC > AZT > FTC > NVP. The fold-increase in EC50 to delay viral rebound was DDI < 4'-Ed4T < LFD4C < FTC < D4T < 3TC < NVP < AZT. The ranking of persistence of anti-HIV activity of the inhibitors based on the two-component assay was DDI > 4'-Ed4T > LFD4C > FTC = D4T > 3TC > NVP > AZT. The persistence ranking was derived from assays based on measures of single viral replication-cycle and cumulative inhibition at multiple time-points. Therefore, a better indicator of the pharmacodynamic property of an inhibitor. The persistence of anti-HIV activity assay may complement in vitro potency assays to better predict in vivo performance of nucleoside analogs.