Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.
Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.
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DOI：
10.1371/journal.pmed.0020249
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发表时间：
2005-08
期刊：
影响因子：
15.8
通讯作者：
Staprans SI
中科院分区：
文献类型：
--
作者：
Regoes RR;Longini IM;Feinberg MB;Staprans SI
猕猴模型试验在评价旨在预防艾滋病毒感染的生物医学干预措施中发挥着至关重要的作用，如疫苗、杀微生物剂和全身化学预防。这些试验通常以非常高的病毒挑战剂量进行，从而肯定会导致感染。然而，这些高挑战剂量并不能真实地反映艾滋病毒在人类中传播的低概率，因此可能会排除预防“现实生活”暴露的预防性干预措施。到目前为止，人们认为，涉及实际低挑战剂量的实验需要大量动物，这阻碍了开发使用高挑战剂量的替代品。利用统计能量分析，我们调查了使用低病毒攻击量进行临床前试验需要多少动物。我们表明，反复用低剂量挑战动物的实验设计不需要不可行的大量动物来评估疫苗或杀微生物剂的成功。使用重复低剂量挑战的临床前试验是确定潜在预防干预措施的一种有前途的替代方法。在动物身上使用反复的低剂量挑战病毒进行艾滋病毒疫苗试验是可行的，而且可能更贴近生活。
Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against “real life” exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses. Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success. Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions. Trials of HIV vaccines in animals using repeated low- dose challenges of the virus are feasible and may be more true to life.
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
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DOI：
10.1098/rstb.1988.0108
发表时间：
1988-10-31
影响因子：
6.3
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通讯作者：
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作者：
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