LA HIV Treatment in Pediatrics

项目摘要 这个拟议项目的长期目标是开发一个创新的，最终用户知情的交付 抗逆转录病毒药物通过幼儿植入系统（DAISY）。DAISY将提供产品组合 超过幼儿（2-5岁）现有口服抗逆转录病毒治疗（ART）的属性： 长期ART（至少6个月）、给药过程中的可逆性、使用者独立性、生物降解，以及 使用的自由裁量权。以南非共和国（RSA）的首选用户特征为重点， DAISY平台旨在延长门诊访视之间的时间，并简化抗逆转录病毒药物（ARV）的给药方案 在幼儿中，最终提高依从性，从而抑制病毒，疾病进展， 儿童发展。如果需要，在ARV输送期间，植入物是唯一可回收的，但 否则在药物耗尽后保持静止和生物降解。以这种方式，逆转药物 在出现不良反应或需要改变治疗方案的情况下，可以进行给药。植入技术 还将药物递送特性与生物降解特性相结合， ARV释放动力学。所提出的具体目标直接涉及这个国家研究所的目标， 用于治疗HIV-1的创新长效药物递送系统的健康机会（RFA-AI-18-057） 被感染的孩子具体目标是：（1）开发DAISY产品，包括抗逆转录病毒制剂、植入剂、 形状因素和生物降解表征;（2）评价安全性、药代动力学和疗效 在新西兰白色兔和非人临床前研究期间， 灵长类动物;（3）通过与最终用户的迭代社会行为研究为技术开发提供信息 在RSA的人口。重要的是，拟议的工作将利用早期计划取得的成就 并将在以下关键方面建立这项工作：长期交付 (up 6个月）的多种抗逆转录病毒药物，并将RSA的最终用户可接受性数据纳入目标 产品简介。我们的研究战略是里程碑驱动的，有明确的预期成果指导进展 以适应未来的临床翻译。

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.