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

描述（由申请人提供）：prevention（暴露前预防病毒进入）是一个综合的临床前/临床项目，其总体目标是提供一套全面的数据，以促进抗病毒凝集素Griffithsin （GRFT）是否应该在局部杀微生物剂开发过程中进行明智的决策。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。我们的产品目标是直肠杀微生物凝胶，含有GRFT作为主要活性药物成分（API）。由于直肠粘膜中HIV靶细胞的高度优势以及通常与RAI相关的粘膜创伤，进行无保护的接受性肛交（URAI）的人是最容易感染HIV-1的人群。作为一种不太可能广泛用于抗逆转录病毒治疗的小蛋白质，GRFT prevention项目与涉及小分子抗逆转录病毒药物（ARV）的暴露前预防（PREP）策略不同，后者具有选择病毒耐药性的潜在风险。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以及HSV-2、HCV和其他由URAI传播的包膜病毒重复感染的艾滋病毒感染者提供了急需的选择。三个项目和四个核心都将有助于整体计划的具体目标。目的1：提供一套全面的安全性和有效性数据，以促进GRFT直肠杀微生物剂进入后期临床研究的进行/不进行决定。目标2：管理和整合预防U19项目与NIH赞助商和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。

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.