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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 局部杀微生物剂是预防艾滋病毒传播和其他性传播感染的一项新兴战略。一种成功的局部杀微生物剂产品将在性交前使用，无需征得伴侣的同意，并将对包括艾滋病毒在内的各种性传播感染有效。在物理特性、可用性、易用性、安全性和有效性方面，它将为潜在用户所接受。 我们利用猕猴阴道安全模型(目前由NIH签约，HHSN266200700013C)为许多正在开发的局部杀微生物剂产品提供标准化的临床前安全数据。在合同模式中，产品安全措施包括宫颈阴道阴道镜检查、阴道微生物评估和阴道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性因素的情况下，阴道环境对重复使用局部产品的反应。 通过这个项目，我们增强了在尾辫猕猴模型中进行的标准化阴道安全性评估，将性行为后和精液存在时的评估包括在内。 在持续的资金支持下，我们正在收集一大批雌性猕猴的基线数据，评估交配前后的宫颈阴道环境。此外，我们正在收集平行的性交前和性交后评估，并使用安慰剂凝胶(HEC通用安慰剂)。 这些研究提供了关于局部使用杀菌剂与性行为有关的迫切需要的数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 the contract model, measures of product safety include cervicovaginal colposcopy, vaginal microbiologic evaluation, and vaginal pH monitoring. The 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. With this project, we have enhanced 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 are collecting baseline data from a large cohort of female macaques assessing the cervicovaginal environment before and after mating. In addition, we are collecting parallel pre- and post-coital assessments, with a placebo gel (HEC universal placebo) in place. These studies provide urgently needed data regarding topical microbicide use with coital activity.