AIDS THERAPIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 通过对非人灵长类动物(NHP)模型的研究，我们对导致艾滋病的病毒以及疾病本身的了解得到了很大程度的提高。人类HIV/AIDS和猴SIV/AIDS之间的许多相似之处为在猴模型中实验研究病毒的致病性和疾病干预策略提供了基础，对人类疾病的理解和治疗具有直接的意义。此外，使用NHP进行临床前药物测试以确认对高度相似的病毒和疾病的有效性的重要性被认为是将这些急需的治疗剂投入人类临床试验的最快实验方法。临床前试验被认为是候选人类药物审批过程中的必要步骤。FDA所谓的“两只动物规则”适用于艾滋病候选药物，根据这一规则，在两个动物模型中证明的安全性和有效性可以立即获得人类使用的许可。NHP被认为是理想的第二或非啮齿动物模型。对于免疫系统附着的感染性病原体来说尤其如此，这些病原体通过穿越粘膜进行感染，就像艾滋病毒一样。原型研究涉及4到6组，每组5或6只动物。在使用抗病毒药物(通常以多种浓度输送给每个治疗组)或模拟治疗后，每组都要接受已证实的病毒库的挑战。药物疗效取决于感染挑战的结果和病毒感染受到限制的程度--相对于模拟治疗的对照。此外，在疗效试验期间对候选药物的局部和全身毒性进行评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A great deal of our understanding of the viruses that cause AIDS as well as the disease itself has been acquired through study of nonhuman primate (NHP) models. Numerous similarities between human HIV/AIDS and simian SIV/AIDS provide the basis to experimentally study virus pathogenicity and disease intervention strategies in simian models with direct implications for the human disease understanding and treatment. Further, the importance of using NHP for preclinical drug testing to confirm efficacy against a highly similar virus and disease is recognized as the quickest experimental method to move these much need therapeutic agents into human clinical trials. Preclinical trials have been deemed a necessary step in the approval process for candidate human drugs. The FDA's so called "two animal rule" applies to candidate AIDS drugs whereby safety and efficacy demonstrated in two animal models could result in immediate licensure for human use. NHP are recognized as the ideal second or non-rodent animal model. This is particularly true for immune system attaching infectious agents that infect by traversing mucous membranes as does HIV. Prototypical studies involve 4 to six groups of 5 or 6 animals. Each group is challenged by a proven virus stock after or concurrently with antiviral (usually delivered in multiple concentrations to each treated group) or mock-treatment. Drug efficacies are determined by the outcomes of the infectious challenges and the degree -with respect to the mock-treated controls that the virus infections are limited. Additionally, local and systemic candidate drug toxicity are evaluated during efficacy trials.