Core B: Antiretroviral Intravaginal Ring Formulation

项目摘要：核心B 高效抗逆转录病毒疗法(HAART)，即联合给予抗逆转录病毒(ARV)药物，具有 成为艾滋病毒/艾滋病治疗的标准。越来越多的人达成共识，抗逆转录病毒药物的组合 这将是艾滋病毒最佳有效的非疫苗生物医学预防(NBP)战略所必需的。 抗逆转录病毒组合的配制和交付的困难限制了确定有效和 安全的NBP产品，用于阴道局部应用。此外，在确定外用药物依从性方面存在困难 杀微生物剂的临床试验限制了这些试验衡量人类艾滋病毒预防效果的能力。 人口。这项IPCP-MBP努力的长期目标是开发阴道内环(IVR)配方 多种抗逆转录病毒药物用于预防艾滋病毒的性传播，强调妇女在 发展中世界。核心B的具体目标是制定一个用于提供抗逆转录病毒药物的静脉注射受体资料库 由FDA批准的药物组成的组合，并将这些配方提供给组成部分项目 项目1--药代动力学(PK)、项目2--安全性、项目3--疗效、项目4-(第一阶段前期) 探索性临床试验。最佳候选组合的选择将通过以下方式完成 一种基于PK、安全性和有效性的迭代配方开发的新筛选过程 结果。这种优化的配方将过渡到项目5，以开发方法和能力，以 制造临床cGMP大量表现最好的GMOS候选IVR。制定工作的努力 在这条多方面的支持IND的关键路径中，将能够推进 最安全和最有效的组合进入IPCP后I期临床试验。为了解决这一困难 在评估依从性治疗中遇到的杀微生物剂试验，一种新的依从性IVR 开发了一种使用温度测量来确定和记录每小时是否佩戴IVR的设备。这个 原型装置将针对女性使用进行优化，并在一项试点临床研究中进行评估。

PROJECT SUMMARY: CORE B Highly Active Antiretroviral Therapy (HAART), where antiretroviral (ARV) drugs are given in combination, has become the standard in treatment of HIV/AIDS. There is growing consensus that combinations of ARV agents are going to be needed for an optimally effective non-vaccine biomedical prevention (nBP) strategy for HIV. Difficulty in formulation and delivery of ARV combinations has limited the ability to determine efficacious and safe nBP products for vaginal topical application. Additionally, difficulty in determining adherence in topical microbicide clinical trials has limited the ability of these trials to measure efficacy of HIV prevention in human populations. The long-term goal of this IPCP-MBP effort is to develop intravaginal ring (IVR) formulations of multiple ARV drugs for prevention of sexual HIV transmission, emphasizing the needs of women in the developing world. The specific objective of Core B is to formulate a library of IVRs for delivering ARV combinations consisting of FDA-approved drugs and to provide these formulations to the component projects of the IPCP: Project 1-pharmacokinetics (PK), Project 2-safety, Project 3-efficacy, Project 4-(pre-Phase I) Exploratory Clinical Trial. Selection of the best performing candidate combination will be accomplished through a novel screening process involving iterative formulation development informed by PK, safety, and efficacy results. This optimized formulation will be transitioned into Project 5 to develop methods and capacity to manufacture clinical cGMP lots of the best performing candidate IVR at GMOs. The formulation efforts throughout this multi-faceted IND-enabling critical path will enable advancement of the lead formulation of the safest and most efficacious combination into post-IPCP Phase I clinical trials. In order to address the difficulty microbicide trials have encountered in assessing adherence to treatment, a novel adherence IVR has been developed that uses temperature measurement to determine and record hourly if an IVR is being worn. The prototype device will be optimized for use in women and evaluated in a pilot clinical study.