IMPROVED MACAQUE SAFETY MODEL FOR TOPICAL MICROBICIDES: POST-COITAL ASSESSMENTS

改进的猕猴外用杀菌剂安全模型：性交后评估

• 批准号: 8172750
• 负责人: DOROTHY L PATTON
• 金额: $ 46.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172750
• 关键词: Attention; Characteristics; Coitus; Colposcopy; Computer Retrieval of Information on Scientific Projects Database; Consent; Contracts; Data; Development; Environment; Epithelial; Evaluation; Exogenous Factors; Female; Funding; Gel; Grant; HIV; Institution; Local Microbicides; Macaca; Measures; Modeling; Monitor; Partner in relationship; Placebos; Prevention strategy; Property; Research; Research Personnel; Resources; Safety; Seminal fluid; Sex Behavior; Sexually Transmitted Diseases; Source; Trauma; United States National Institutes of Health; Vagina; improved; preclinical evaluation; preclinical safety; response; transmission process

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. Topical microbicides represent an emerging strategy for the prevention of transmission of HIV and other sexually transmitted infections. A successful topical microbicide product will be applied prior to intercourse, without necessitating partner consent, and will be active against a variety of STIs, including HIV. It will be acceptable to potential users in terms of physical characteristics, availability, ease of use, safety and efficacy properties. We have utilized the macaque vaginal safety model (currently contracted by the NIH, HHSN266200700013C) to provide standardized preclinical safety data for numerous topical microbicide products in development. In this model, measures of product safety include cervicovaginal colposcopy, vaginal microbiologic evaluation, and vaginal pH monitoring. This model characterizes the vaginal environment's response to repeated topical product applications in the absence of the exogenous factors of intercourse and potentially infectious ejaculate. While our preclinical evaluations of topical microbicide products have been well-rounded in many aspects, we have yet to investigate the effects of sexual intercourse on the cervicovaginal environment. Mucosal perturbation and potential micro-trauma in the form of epithelial abrasions are likely to result from sexual activity. Additionally, the effects that seminal fluid may induce on the cervicovaginal environment, as well as its effects vis-a vis topical microbicide product safety and efficacy, have not yet received their due attention. We propose to enhance our standardized vaginal safety evaluations conducted in the pigtailed macaque model to include evaluations after sexual activity and with the presence of seminal fluid. With continued funding, we will collect baseline data from 24 female macaques assessing the cervicovaginal environment before and after mating. In addition, we will collect parallel assessments, when mating has occurred with a placebo gel (HEC universal placebo) in place. These studies will provide urgently needed data regarding topical microbicide use with coital activity.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 外用杀菌剂代表了预防艾滋病毒和其他性传播感染传播的新兴策略。成功的外用杀菌剂产品将在性交前使用，无需伴侣同意，并且可有效对抗多种性传播感染，包括艾滋病毒。它在物理特性、可用性、易用性、安全性和功效特性方面将被潜在用户所接受。 我们利用猕猴阴道安全模型（目前由 NIH 签约，HHSN266200700013C）为正在开发的众多外用杀菌剂产品提供标准化的临床前安全数据。在此模型中，产品安全措施包括宫颈阴道阴道镜检查、阴道微生物学评估和阴道 pH 值监测。该模型描述了在没有性交和潜在感染性射精的外源因素的情况下，阴道环境对重复局部产品应用的反应。虽然我们对外用杀菌剂产品的临床前评估在许多方面都很全面，但我们尚未调查性交对宫颈阴道环境的影响。粘膜扰动和上皮擦伤形式的潜在微创伤可能是由性活动引起的。此外，精液可能对宫颈阴道环境产生的影响，以及其相对于局部杀菌剂产品的安全性和功效的影响，尚未得到应有的关注。我们建议加强在猪尾猕猴模型中进行的标准化阴道安全评估，包括性活动后和精液存在下的评估。 通过持续的资助，我们将收集 24 只雌性猕猴的基线数据，评估交配前后的子宫颈阴道环境。此外，当使用安慰剂凝胶（HEC 通用安慰剂）进行交配时，我们将收集平行评估。 这些研究将提供有关性交活动中局部杀菌剂使用的迫切需要的数据。