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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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种新兴战略。一种成功的局部杀微生物剂产品将在性交前使用，无需伴侣同意，并将对各种性传播疾病，包括艾滋病毒有效。在物理特性、可用性、易用性、安全性和有效性方面，潜在用户可接受。 我们利用猕猴阴道安全模型（目前由NIH承包，HHSN 266200700013 C）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性数据。在合同模式中，产品安全性的措施包括宫颈阴道镜检查、阴道微生物评价和阴道pH值监测。该模型的特点阴道环境的反应，反复局部产品的应用程序在没有外源性因素的性交和潜在的传染性射精。 通过该项目，我们加强了在猪尾猕猴模型中进行的标准化阴道安全性评价，包括性活动后和精液存在时的评价。 在持续的资金支持下，我们正在收集大量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）。 这些研究提供了迫切需要的数据，关于局部杀微生物剂的使用与性交活动。

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.