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

描述（由申请人提供）：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来预防全球范围内的艾滋病毒传播。由于这一流行病的蔓延速度之快，国际社会必须扩大由女性控制的预防办法，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。我们的印度合作者开发了一种名为“BASANT”的多草药阴道杀菌剂，可以抑制包括艾滋病毒在内的多种性传播病原体。在印度进行的一期和二期人体试验中，初步研究也显示出安全性和可接受性。因此，我们在这项应用中的目标是验证Basant在体内预防HIV传播的有效性。这些研究的中心目标是确定Basant在人源化小鼠模型中预防阴道内/直肠内HIV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），并在此过程中可能开发出最有效的抗HIV-1阴道内/直肠内杀微生物剂。此外，Basant的功效将针对6种主要的全球流行的HIV-1分离株进行评估，这些分离株的遗传和生物学特征可能有助于预防世界不同发展中国家/发达国家的HIV传播。最后，我们将进行体外实验，以表征HIV-1在抑制剂Basant的选择压力下使用的逃逸途径。Basant将用于产生候选逃避突变体，以对抗来自不同遗传亚型的广泛R5 HIV-1分离株。这项研究具有高度的创新性和意义，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微生物剂的开发。使用阴道杀微生物剂可减少每次接触的风险，可能对减少艾滋病毒传播产生巨大影响。这项研究具有高度的创新性和意义，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微生物剂的开发。使用阴道杀微生物剂可减少每次接触的风险，这可能对在全球范围内减少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.