Preclinical User Accptability Studies Long Acting Vaginal Gels, Intravaginal Ring

在防治艾滋病毒/艾滋病的斗争中，必须研制安全、有效和可接受的杀微生物剂。 杀微生物剂产品的成功将来自于其生物功能和使用者的协同作用。 可接受性生物功能性是安全有效的抗HIV化合物的综合结果 将这些化合物掺入成功地将这些化合物递送至靶组织、流体 和病原体。可接受性是一个多因素的现象，它解释了个人的，二元的，产品相关的 和社会环境，增强-或不-妇女的决定，使用杀微生物剂。接受性 强烈依赖于具有生物物理功能和/或机械和材料的递送系统 最有利于人类使用的特性。如果没有这两者，杀微生物剂对公众的潜在影响 艾滋病毒/艾滋病健康危机将在很大程度上受到限制。项目3将整合和扩展我们不断增长的知识 临床前杀微生物剂配方和输送装置科学的方法学， 在早期的人类可接受性研究中。它将扩展目前研究凝胶的行为策略 在临床前框架中的可接受性，并将这些策略扩展到阴道内环（IVR）应用。 项目3将首先修改现有的行为工具，测量局部凝胶可接受性尺寸， 临床前制剂开发;新工具将纳入扩展的可接受性维度， 说明使用长效凝胶和IVR设备在这个U19开发。然后我们将扩展我们的 目前临床前体内人体研究方法，将成像实验与行为 考核这将有助于共同确定杀微生物剂成功的两个关键组成部分： 可接受性和凝胶功能性。此外，我们将使用扩展的措施来分析 行为测量和生物物理测量之间的对应，创建统计框架 从而能够从凝胶性能测量中预测长效凝胶体验的用户评级。最后， 我们将检查用户对与这些输送系统相关的可接受性维度的评分， 提出长效凝胶和IVRs可接受性的初始临床前标准。

The development of safe, effective and acceptable microbicides is imperative in the fight against HIV/AIDS. The success of microbicide products will derive from the synergy of their biological functionality and user acceptability. Biological functionality is the integrated result of safe and effective anti-HIV compounds incorporated into formulations or devices that successfully deliver those compounds to target tissues, fluids and pathogens. Acceptability is a multi-factorial phenomenon that accounts for the personal, dyadic, productrelated and social contexts that potentiate - or not - a woman's decision to use a microbicide. Acceptability depends strongly upon delivery systems with biophysical functions and /or mechanical and materials properties that are most conducive to human use. Without both, microbicides' potential to impact the public health crisis of HIV/AIDS will be largely limited. Project 3 will integrate and extend our growing knowledge and methodologies in preclinical microbicide formulation and delivery device sciences, with their counterpart in early human studies of acceptability. It will extend current behavioral strategies for studying gel acceptability in preclinical frameworks, and expand those strategies to intravaginal ring (IVR) applications. Project 3 will first modify existing behavioral tools that measure topical gel acceptability dimensions for preclinical formulation development; the new tools will incorporate expanded acceptability dimensions to account for the use of long-acting gels and IVR devices developed in this U19. We will then extend our current preclinical in vivo human studies methodology, integrating imaging experiments with behavioral assessment. This will enable joint determination of two critical components of microbicide success: user acceptability and gel functionality. Further, we will use the expanded measures to analyze the correspondence between behavioral measures and biophysical measures, creating a statistical framework enabling prediction of user ratings of long-acting gel experiences from gel performance measures. Finally, we will examine user ratings of acceptability dimensions associated with these delivery systems, and propose initial preclinical standards of acceptability for long-acting gels and IVRs.