Griffithsin-based Rectal Microbicides for PREvention of Viral ENTry (PREVENT)

描述(由申请人提供)：预防(暴露前预防病毒进入)是一项综合的临床前/临床计划，总体目标是提供一组全面的数据，以促进关于抗病毒凝集素Griffithsin(GRFT)是否应该在局部杀菌剂管道中取得进展的知情决定。GRFT对人类免疫缺陷病毒(HIV)1型和2型、单纯疱疹病毒2型(HSV-2)和丙型肝炎病毒(HCV)具有广谱活性。我们的产品目标是一种直肠杀微生物剂凝胶，含有GRFT作为主要活性药物成分(API)。实行无保护的接受性肛交(URAI)的人代表了最容易受到HIV-1传播的人群，因为直肠粘膜中HIV靶细胞的高优势，以及通常与RAI相关的粘膜损伤。作为一种小蛋白，GRFT预防计划不同于暴露前预防(PREP)策略，后者涉及小分子抗逆转录病毒(ARV)，后者承担选择病毒耐药性的潜在风险。由含有GRFT的润滑剂凝胶提供的广谱抗病毒预防，为需要有效预防艾滋病毒重叠感染以及由尿路感染传播的HSV-2、丙型肝炎病毒和其他包膜病毒的艾滋病毒感染者提供了亟需的选择。三个项目和四个核心都将有助于实现整个方案的具体目标。目的1：提供一套全面的安全性和有效性数据，以促进GRFT直肠杀菌剂进入后期临床研究的进行/不进行的决定。目标2：将预防U19计划与NIH赞助商以及GRFT杀微生物剂凝胶产品的未来赞助商和投资者的目标和期望进行管理和整合。

DESCRIPTION (provided by applicant): PREVENT (Pre-exposure prevention of viral entry) is an Integrated Preclinical/Clinical Program, with the overall goal to provide a comprehensive set of data to facilitate an informed decision on whether the antiviral lectin Griffithsin (GRFT) shoul progress in the topical microbicides pipeline. GRFT has broad-spectrum activity against human immunodeficiency viruses (HIV) types 1 and 2, herpes simplex virus type 2 (HSV-2) and hepatitis C virus (HCV). Our product target is a rectal microbicide gel, containing GRFT as the primary Active Pharmaceutical Ingredient (API). People who practice unprotected receptive anal intercourse (URAI) represent the population most vulnerable to HIV-1 transmission due to the high preponderance of HIV target cells in the rectal mucosa, and mucosal trauma commonly associated with RAI. As a small protein, unlikely to be widely used in antiretroviral therapy, the GRFT PREVENT program stands apart from pre-exposure prophylaxis (PREP) strategies that involve small molecule antiretrovirals (ARV), which bear the potential risk of selecting for viral resistance. Broad spectrum antiviral prophylaxis that is offered by lubricant gels containing GRFT offer a much needed option for HIV infected people who require effective PREP against superinfection with HIV as well as HSV-2, HCV and other enveloped viruses that are transmitted by URAI. Three Projects and four Cores will all contribute to the Specific Aims of the Overall Program. Aim 1: Provide a comprehensive set of safety and efficacy data to facilitate a Go/No-Go decision on progression of GRFT rectal microbicides into later stage clinical studies. Aim 2: Manage and integrate the PREVENT U19 Program with the goals and expectations of the NIH sponsor and future sponsors and investors in GRFT microbicide gel products.