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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 局部微生物代表了预防HIV传播和其他性传播感染的新兴策略。无需伴侣同意，将在交往之前使用成功的局部杀菌剂产品，并且将对包括艾滋病毒在内的各种性传播感染进行活跃。在物理特征，可用性，易用性，安全性和功效属性方面，潜在用户可以接受。 我们利用了猕猴的阴道安全模型（目前由NIH，HHSN266200700013C签约）为开发中许多局部菌皮产品提供了标准化的临床前安全数据。在此模型中，产品安全性的测量包括宫颈阴道阴道镜检查，阴道微生物学评估和阴道pH监测。该模型表征了阴道环境对不存在性交的外源性因素和潜在感染性射精的反复局部产品应用的反应。虽然我们对局部杀微生物产品的临床前评估在许多方面都广泛，但我们尚未研究性交对宫颈阴道环境的影响。上皮擦伤形式的粘膜扰动和潜在的微创伤可能是性活动引起的。此外，精液液可能诱导宫颈阴道环境的影响及其相对于局部杀微生物的产品安全性和功效的影响尚未得到适当的关注。我们建议增强在辫子猕猴模型中进行的标准化阴道安全评估，以包括性活动后的评估以及出现精确的液体。 通过持续的资金，我们将从24个女猕猴中收集基线数据，评估交配前后的子宫颈阴道环境。此外，当与安慰剂凝胶（HEC通用安慰剂）发生交配时，我们将收集并行评估。 这些研究将提供有关局部用菌心使用和同性活动活性的急需数据。