Ronen Keshet, Sharma Amit, Overbaugh Julie
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
AIDS. 2015 Nov;29(17):2219-2227. doi: 10.1097/QAD.0000000000000845.
Rigorous testing of new HIV-prevention strategies is a time-consuming and expensive undertaking. Thus, making well informed decisions on which candidate-prevention approaches are most likely to provide the most benefit is critical to appropriately prioritizing clinical testing. In the case of biological interventions, the decision to test a given prevention approach in human trials rests largely on evidence of protection in preclinical studies. The ability of preclinical studies to predict efficacy in humans may depend on how well the model recapitulates key biological features of HIV transmission relevant to the question at hand. Here, we review our current understanding of the biology of HIV transmission based on data from animal models, cell culture, and viral sequence analysis from human infection. We summarize studies of the bottleneck in viral transmission; the characteristics of transmitted viruses; the establishment of infection; and the contribution of cell-free and cell-associated virus. We seek to highlight the implications of HIV-transmission biology for development of prevention interventions, and to discuss the limitations of existing preclinical models.
对新型艾滋病预防策略进行严格测试是一项耗时且昂贵的工作。因此，就是否最有可能带来最大益处做出明智的决策对于合理安排临床试验的优先级至关重要。对于生物干预措施而言，在人体试验中测试特定预防方法的决定很大程度上取决于临床前研究中的保护证据。临床前研究预测人体疗效的能力可能取决于该模型对与手头问题相关的艾滋病病毒传播关键生物学特征的重现程度。在此，我们基于来自动物模型、细胞培养和人类感染病毒序列分析的数据，回顾我们目前对艾滋病病毒传播生物学的理解。我们总结了病毒传播瓶颈、传播病毒的特征、感染的建立以及游离病毒和细胞相关病毒的作用的研究。我们试图强调艾滋病病毒传播生物学对预防干预措施开发的影响，并讨论现有临床前模型的局限性。
