LA HIV Treatment in Pediatrics

项目总结 这个拟议项目的长期目标是开发一种创新的、终端用户知情的交付 通过幼儿植入性系统使用抗逆转录病毒药物(DAISY)。黛西将提供一系列产品组合 用于幼儿(2-5岁)的抗逆转录病毒治疗(ART)超过现有口服方案的属性： 长期抗逆转录病毒治疗(至少6个月)，给药过程中的可逆性，使用者的独立性，生物降解，以及 自由裁量权。以南非共和国(RSA)的首选用户特征为重点， DAISY平台旨在延长就诊之间的时间间隔，并简化抗逆转录病毒药物(ARV)的给药方案 最终改善依从性，从而提高病毒抑制、疾病进展和 童年发展。如果需要，在ARV交付期间，植入物是唯一可回收的，但是 否则保持静止并在药物耗尽后生物降解。就这样，药物的逆转 在出现不良反应或需要改变方案的情况下，可以分娩。植入物技术 还将药物输送特性与生物降解特性分离，并可实现零级 抗逆转录病毒药物释放动力学研究。提议的具体目标直接解决了这个国家研究院的目标 用于HIV-1治疗的创新长效给药系统的健康机会(RFA-AI-18-057) 受感染的儿童。具体目标是(1)开发DAISY产品，包括ARV配方、植入物 形式因素和生物降解的特征；(2)评估安全性、药代动力学和疗效 新西兰白兔和非人类临床前研究中向下选择的雏菊原型 灵长类动物；以及(3)通过与最终用户的迭代社会行为研究为技术发展提供信息 RSA中的种群。重要的是，拟议的工作将利用在早期计划中取得的成就 在开发植入物平台方面，将在以下关键方面加强这项工作：长期交付 (最多6个月)多个ARV，并将来自RSA的最终用户可接受性数据整合到目标中 产品简介。我们的研究战略是里程碑式的，以明确的预期成果指导进展 与未来的临床翻译保持一致。

PROJECT SUMMARY The long-term goal of this proposed project is to develop an innovative, end-user informed Delivery of Antiretrovirals via Implantable System for Young children (DAISY). DAISY will offer a combination of product attributes that surpass existing oral regimens for antiretroviral treatment (ART) in young children (ages 2-5): long-term ART (at least 6 months), reversibility during drug delivery, user independence, biodegradation, and discretion of use. With a focus on preferred user characteristics in the Republic of South Africa (RSA), the DAISY platform aims to extend time between clinic visits and simplify dosing regimens of antiretrovirals (ARVs) in young children to ultimately improve adherence, and thus, viral suppression, disease progression, and childhood development. The implant is uniquely retrievable, if needed, for the duration of ARV delivery, but otherwise remains stationary and biodegrades after depletion of the drug. In this manner, reversal of drug delivery is possible in the case of adverse reactions or need to change in the regimen. The implant technology also decouples drug delivery characteristics from biodegradation properties and can achieve zero-order kinetics of ARV release. The proposed specific aims directly address the goals of this National Institutes of Health opportunity (RFA-AI-18-057) for innovative long-acting drug delivery systems for treatment of HIV-1 infected children. The specific aims are to (1) develop the DAISY product, including ARV formulations, implant form factors, and characterization of biodegradation; (2) evaluate safety, pharmacokinetics, and efficacy of down-selected DAISY prototypes during preclinical studies in New Zealand White rabbits and nonhuman primates; and (3) inform technology development via iterative socio-behavior research with end-user populations in RSA. Importantly, the proposed work will leverage achievements made during earlier programs in developing the implant platform and will build on this work in the following key aspects: long-term delivery (up to 6 months) of multiple ARVs and incorporation of end-user acceptability data from RSA into a Target Product Profile. Our Research Strategy is milestone-driven, with clear expected deliverables guiding progress of product development to align with future clinical translation.