Evaluation of efficacy of a polyherbal (Basant) anti-HIV vaginal microbicide in h

说明(申请人提供)：在缺乏疫苗的情况下，迫切需要一种有效的局部杀微生物剂，以防止艾滋病毒在世界范围内的传播。由于疫情蔓延的速度，国际社会必须扩大女性控制的预防选择，例如使用杀微生物剂。我们的长期目标是制定能够限制或预防艾滋病毒传播的有效战略。我们的印度合作者已经开发出一种名为“巴生特”的多草本阴道杀菌剂，它可以抑制包括艾滋病毒在内的多种性传播病原体。初步研究还表明，在印度进行的第一阶段和第二阶段人体试验中，该药物是安全和可接受的。因此，我们在这一应用中的目的是验证巴桑特在预防艾滋病毒体内传播方面的有效性。我们这些研究的中心目标是确定巴桑特在人源化小鼠模型中预防艾滋病毒经阴道/直肠内传播的有效性(特定目标1)，并了解杀微生物剂抗HIV作用的机制(特定目标2)，并在此过程中可能有助于开发最有效的抗HIV-1阴道/直肠内杀菌剂。此外，还将评估巴桑特对六种主要的全球流行的具有遗传和生物学特征的艾滋病毒-1分离株的疗效，这些分离株可能有助于防止艾滋病毒在世界不同的发展中国家/发达国家传播。最后，我们将进行体外实验，以表征HIV-1在抑制剂巴桑特的选择压力下使用的逃逸途径。Basant将用于产生候选逃逸突变株，以对抗来自不同基因亚型的广泛的R5HIV-1分离株。这项研究具有很高的创新性和重大意义，因为从这项研究中获得的新知识可能会导致具有公共卫生意义的新型抗病毒杀菌剂的开发。使用可降低每次接触风险的阴道杀微生物剂，可能会对减少艾滋病毒传播产生巨大影响。这项研究具有很高的创新性和重大意义，因为从这项研究中获得的新知识可能会导致具有公共卫生意义的新型抗病毒杀菌剂的开发。使用可降低每次接触风险的阴道杀微生物剂，很可能对减少全球艾滋病毒传播产生巨大影响。

DESCRIPTION (provided by applicant): In the absence of a vaccine, there is an urgent need for an effective topical microbicide for the prevention of HIV transmission worldwide. Because of the speed at which the epidemic has spread, it is crucial for the global community to expand female-controlled preventive options such as the use of microbicides. Our long-term goal is to develop effective strategies that can restrict or prevent HIV transmission. Our Indian collaborators have developed a polyherbal vaginal microbicide named "BASANT" that inhibits a wide range of sexually transmitted pathogens including HIV. The preliminary studies have also shown safety and acceptability in Phase I and Phase II human trials in India. Therefore, our objective in this application is to verify the effectiveness of the Basant in preventing HIV transmission in vivo. Our central goal of these studies is to determine the efficacy of a Basant in preventing intravaginal/intrarectal HIV transmission in humanized mouse model (Specific objective 1) and to understand the mechanism of microbicide anti-HIV action (Specific objective 2) and in the process may enable for the development of most effective anti-HIV-1 intravaginal/intrarectal microbicide. In addition, the efficacy of Basant will be evaluated against six major globally prevalent strains of genetically and biologically characterized HIV-1 isolates that may help to prevent HIV transmission in different developing/developed countries of the World. Finally, we will conduct in vitro experiments to characterize the escape pathways used by HIV-1 under the selection pressure of an inhibitor, Basant. Basant will be used to generate candidate escape mutants against a broad range of R5 HIV-1 isolates from different genetic subtypes. The proposed research is highly innovative and significant, because the new knowledge gained from this study may lead to the development of novel antiviral microbicides with public health significance. The use of vaginal microbicide that reduce the risk per exposure is likely to exert a tremendous effect on the reduction of HIV transmission. The proposed research is highly innovative and significant, because the new knowledge gained from this study may lead to the development of novel antiviral microbicides with public health significance. The use of vaginal microbicide that reduce the risk per exposure is likely to exert a tremendous effect on the reduction of HIV transmission on a global basis.