Microbicide safety/efficacy studies in animals: macaques and small animal models.
Microbicide safety/efficacy studies in animals: macaques and small animal models.
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DOI：
10.1097/coh.0b013e32830891bb
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发表时间：
2008-09
影响因子：
4.1
通讯作者：
Veazey RS
中科院分区：
文献类型：
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作者：
Veazey RS
一些候选杀微生物剂在人体临床试验中未能预防艾滋病毒传播，而且该领域还不确定能支持多少额外的试验。无论如何，有太多的候选杀微生物剂正在开发中，迫切需要一种逻辑和一致的方法来筛选和选择人体临床试验的候选药物。然而，HIV独特的宿主和细胞特异性为杀微生物剂安全性和有效性筛选提供了挑战，这只能通过在相关实验室动物模型中进行严格测试来解决。从啮齿动物到非人灵长类动物的许多实验室动物模型系统，以及单剂量与多剂量挑战最近已被开发用于测试杀微生物剂候选物。这些模型揭示了候选杀微生物剂的安全性和有效性以及传播的早期机制。本文综述了用于杀菌剂安全性和有效性试验的相关动物模型的主要优缺点。目前，非人灵长类动物是筛选杀微生物剂候选物的唯一相关和有效的实验室模型。鉴于先前策略的一贯失败，现在很明显，在非人灵长类动物中进行严格的安全性和有效性测试应该是将其他杀微生物剂候选物推向人类临床试验的先决条件。
A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. However, the unique host and cell specificity of HIV provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a pre-requisite for advancing additional microbicide candidates to human clinical trials.