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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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性模型（目前由NIH签订合同，编号N 01-AI-95388）为正在开发的许多局部杀微生物剂产品提供标准化的临床前安全性数据。在该模型中，产品安全性的指标包括宫颈阴道镜检查、阴道微生物评价和阴道pH值监测。该模型描述了在没有性交和潜在传染性射精的外源性因素的情况下，阴道环境对重复局部产品应用的反应。虽然我们对局部杀微生物剂产品的临床前评价在许多方面都很全面，但我们还没有研究性交对宫颈阴道环境的影响。粘液扰动和上皮擦伤形式的潜在微创伤可能是性活动引起的。此外，精液可能对宫颈阴道环境产生的影响，以及其维斯局部杀微生物剂产品安全性和有效性的影响，尚未得到应有的重视。我们建议加强我们在马尾猕猴模型中进行的标准化阴道安全性评价，以包括性活动后和精液存在下的评价。 在持续的R33资助下，我们将收集24只雌性猕猴的基线数据，评估交配前后的宫颈阴道环境。此外，我们将在使用安慰剂凝胶（HEC通用安慰剂）进行交配时收集平行评估。 这些研究将提供迫切需要的数据，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. 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, N01-AI-95388) 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 R33 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.