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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。在这个模型中，产品安全性的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性因素的情况下，阴道环境对重复使用局部产品的反应。虽然我们对局部杀微生物剂产品的临床前评估在许多方面都很全面，但我们还没有调查性交对宫颈阴道环境的影响。粘膜紊乱和上皮擦伤形式的潜在微损伤很可能是性行为造成的。此外，精液可能对宫颈阴道环境产生的影响，以及它对局部杀菌剂产品的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。 在继续的资助下，我们将收集24只雌性猕猴的基线数据，评估交配前和交配后的宫颈阴道环境。此外，我们将收集与安慰剂凝胶(HEC通用安慰剂)发生交配时的平行评估。 这些研究将提供有关局部使用杀菌剂与性交活动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. 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.