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

项目摘要/摘要 这一拟议方案的总体目标是开发一种创新的、终端用户知情的艾滋病毒预 暴露预防(PrEP)产品作为可接受的多用户生物降解缓释剂 (琥珀色)植入物。植入物技术解决了当前PrEP药物输送的多重挑战 系统(DDS)通过提供有益的属性：用户独立性和自由使用、零序 聚合物的(持续)释放、长期保护(≤1年)、可回收和生物降解 植入。我们建议将植入物设计成在整个药物递送期间都可以收回，在 不良反应或最终用户希望停止使用的情况。否则，琥珀植入物将保留 药物耗尽后就地和生物降解。独特的是，琥珀植入物使药物输送功能脱钩 从生物降解性，这使得药物释放的零级动力学。琥珀计划 阐述了美国国立卫生研究院(NIH)机会(RFA-AI-19-063)的目标 新型(非)HIV PrEP缓释/缓释DDS的研制 替诺福韦)抗病毒药物(ARV)。我们将通过从以下方面获得偏好洞察力来为植入物开发提供信息 两个优先地理区域的不同性别、性取向和族裔/种族少数群体 在美国的“结束艾滋病毒流行”倡议下。我们提出了三个具体目标：(1)发展 琥珀植入物，聚合物经过优化，具有高耐用性和生物侵蚀特性；(2)精选配方 在临床前研究中评估琥珀铅植入物的安全性、药动学和有效性； (3)确定首选用户特征(PUC)，告知技术开发和未来部署 通过对年轻MSM、顺式和反式MSM进行迭代社会行为研究，将琥珀付诸实践 加利福尼亚州和阿拉巴马州的性别女性。我们将努力使PUC和关键可修改属性在 产品开发：持续(≤1年)交付新型抗逆转录病毒药物，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配置文件 (TPP)，以及在非人灵长类动物模型中的疗效评估。琥珀计划是里程碑式的， 为产品开发工作提供明确的交付成果，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.