LA HIV Treatment in Pediatrics

洛杉矶儿科艾滋病毒治疗

基本信息

批准号：
10546217
负责人：
Mackenzie Cottrell
金额：
$ 149.4万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-15 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10546217
关键词：
5 year old Achievement Address Adherence Adolescent Adverse reactions Age Animal Model Anti-Retroviral Agents Biodegradation Caregivers Characteristics Child Childhood Clinic Visits Data Deoxycytidine Development Devices Disease Progression Dose Drug Delivery Systems Drug Kinetics Effectiveness Engineering Excision Female Formulation Future Goals HIV HIV Seropositivity HIV antiretroviral HIV-1 Health Personnel Healthcare Systems Implant In Vitro Integrase International Intervention Kinetics Lamivudine Link Macaca mulatta Measures New Zealand North Carolina Nucleosides Oral Oryctolagus cuniculus Palate Pattern Pediatrics Pharmaceutical Preparations Phase Population Prevention Principal Investigator Property Qualitative Methods RNA-Directed DNA Polymerase Regimen Research Research Personnel Role Safety Science Social Behavior South Africa System Tail Technology Tenofovir Testing Time Treatment Protocols United States National Institutes of Health Universities Viral Work analog antiretroviral therapy biodegradable polymer clinical practice clinical translation design drug release kinetics drug release profile emtricitabine future implementation implant design improved in vivo industry partner inhibitor innovation male manufacturing process multidisciplinary nonhuman primate pediatric human immunodeficiency virus pre-clinical preclinical study preference product development programs prototype safety testing social stigma subcutaneous technology development

项目摘要

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.

项目概要该拟议项目的长期目标是开发一种创新的、最终用户知情的交付方式通过幼儿植入系统（DAISY）进行抗逆转录病毒治疗。 DAISY 将提供产品组合优于幼儿（2-5 岁）现有抗逆转录病毒治疗 (ART) 口服疗法的特性：长期 ART（至少 6 个月）、药物输送过程中的可逆性、用户独立性、生物降解性和使用的自由裁量权。重点关注南非共和国 (RSA) 的首选用户特征， DAISY 平台旨在延长就诊间隔时间并简化抗逆转录病毒药物 (ARV) 的给药方案最终提高幼儿的依从性，从而抑制病毒、疾病进展和童年发展。如果需要，在抗逆转录病毒治疗期间，植入物是唯一可回收的，但是否则在药物耗尽后保持静止并生物降解。这样，药物的逆转如果发生不良反应或需要改变治疗方案，则可以进行分娩。植入技术还将药物输送特性与生物降解特性解耦，并可以实现零级 ARV 释放动力学。拟议的具体目标直接涉及该国立研究院的目标用于治疗 HIV-1 的创新长效药物输送系统的健康机会 (RFA-AI-18-057) 受感染的儿童。具体目标是（1）开发DAISY产品，包括ARV制剂、植入物形状因素和生物降解特性； (2) 评价药物的安全性、药代动力学和疗效在新西兰白兔和非人类的临床前研究中下调了 DAISY 原型的选择灵长类动物； (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 RSA 中的人群。重要的是，拟议的工作将利用早期计划取得的成就开发植入物平台并将在以下关键方面继续开展这项工作：长期交付（最多 6 个月）多种 ARV 并将来自 RSA 的最终用户可接受性数据纳入目标产品简介。我们的研究策略是里程碑驱动的，有明确的预期交付成果来指导进展产品开发与未来的临床转化保持一致。