Acceptable Multi-user Biodegradable Extended Release (AMBER) Implant System for HIV Prevention

项目概要/摘要 这项拟议计划的总体目标是开发一个创新的，最终用户知情的艾滋病毒预防， 暴露预防（PrEP）产品作为可接受的多用户生物可降解缓释剂 （琥珀色）植入物。植入技术解决了当前PrEP药物输送的多重挑战 通过提供有益的属性：用户独立性和使用的自由裁量权，零阶 （持续）释放，长期保护（≤1年），可回收性和生物降解的聚合物 植入我们建议将植入物设计为在整个药物输送期间可回收， 出现不良反应或最终用户希望停用。否则，琥珀植入物 并在药物耗尽后生物降解。独特的是，琥珀植入物具有药物输送功能 从生物降解性能，这使得零级动力学的药物释放。琥珀计划 解决了美国国立卫生研究院（NIH）机会（RFA-AI-19-063）的目标， 开发用于HIV PrEP的新型和创新的缓释/缓释（SER）DDS， 基于替诺福韦的）抗病毒药物（ARV）。我们将通过从以下方面获取偏好见解来告知植入物开发 在两个优先地理区域内的不同性别、性取向和少数民族/种族人口 在美国发起的“终结艾滋病流行”计划下。我们提出三个具体目标：（1）发展 AMBER植入物具有针对高耐久性和生物侵蚀特征而优化的聚合物;（2） 抗逆转录病毒药物，并在临床前研究中评估铅琥珀植入物的安全性、药代动力学和有效性; (3)确定首选用户特征（PUC），为技术开发和未来部署提供信息， 通过对年轻的男男性接触者，顺式和反式进行反复的社会行为研究， 加州和亚拉巴马的女性。我们将努力使PUC和关键可修改属性保持一致， 产品开发：新型抗逆转录病毒药物的持续（≤1年）交付，聚合物旨在优化 生物降解时间表，将最终用户可接受性信息纳入目标产品概况 (TPP)以及在非人灵长类动物模型中的功效评价。琥珀计划是里程碑驱动的， 为产品开发工作提供定义的可交付成果，以支持临床翻译的未来需求。

PROJECT SUMMARY/ABSTRACT The overarching goal of this proposed program is to develop an innovative, end-user informed HIV pre- exposure prophylaxis (PrEP) product as an Acceptable Multi-user Biodegradable Extended Release (AMBER) implant. The implant technology addresses multiple challenges with current PrEP drug delivery systems (DDS) by offering beneficial attributes: user-independence and discretion of use, zero-order (sustained) release, long-term protection (≤1 year), retrievability and biodegradation of the polymeric implant. We propose to engineer the implant to be retrievable throughout the drug delivery period, in the case of adverse reactions or an end-user’s wish to discontinue. Otherwise, the AMBER implant will remain in-place and biodegrade after drug depletion. Uniquely, the AMBER implant decouples drug delivery features from biodegradation properties, which enables zero-order kinetics of drug release. The AMBER program addresses the goals of this National Institutes of Health (NIH) opportunity (RFA-AI-19-063) for the development of new and innovative sustained/extended release (SER) DDS for HIV PrEP with novel (non- tenofovir based) antivirals (ARV). We will inform implant development by eliciting preference insights from diverse gender, sexual orientation, and ethnic/racial minority populations in two priority geographical areas under “Ending the HIV Epidemic” initiative in the United States. We propose three specific aims: (1) develop the AMBER implant with polymers optimized for high durability and bioerosion profiles; (2) formulate selected ARVs and evaluate safety, pharmacokinetics, and efficacy of lead AMBER implants in preclinical studies; (3) identify Preferred User Characteristics (PUCs), inform technology development and future deployment of AMBER into practice by conducting iterative socio-behavioral research with Young MSM, cis- and trans- gender women in California and Alabama. We will strive to align PUC and key modifiable attributes during product development: sustained (≤1 year) delivery of novel ARV, polymers designed to optimize biodegradation timescales, incorporation of end-user acceptability information into a Target Product Profile (TPP), and evaluation of efficacy in nonhuman primate model. The AMBER program is milestone-driven and provides defined deliverables to product development efforts to support future needs in clinical translation.