LA HIV Treatment in Pediatrics

洛杉矶儿科艾滋病毒治疗

• 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
• 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

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.

项目摘要 这个拟议项目的长期目标是开发创新的，最终用户的知情交付 抗逆转录病毒通过幼儿的植入系统（Daisy）。雏菊将提供产品的组合 超过幼儿抗逆转录病毒治疗（ART）现有口服方案的属性（2-5岁）： 长期艺术（至少6个月），药物输送期间的可逆性，用户独立性，生物降解和 使用的酌处权。重点是南非共和国（RSA）首选用户特征， 雏菊平台旨在延长诊所就诊之间的时间，并简化抗逆转录病毒的给药方案（ARVS） 在幼儿中，最终提高依从性，从而提高病毒抑制，疾病进展和 儿童发展。在ARV交付期间，植入物是可唯一可检索的，但是 否则，药物耗尽后仍保持静止和生物降解。通过这种方式，毒品逆转 如果不良反应或需要改变方案，则可以传递。植入技术 还可以将药物输送特性从生物降解特性中脱离，并且可以达到零级 ARV释放动力学。拟议的具体目的直接解决了该国立机构的目标 健康机会（RFA-AI-18-057）用于治疗HIV-1的创新长效药物输送系统 感染的儿童。具体目的是（1）开发雏菊产品，包括ARV配方，植入物 形式和生物降解的表征； （2）评估安全性，药代动力学和功效 在新西兰白兔子和非人类的临床前研究期间，下降的雏菊原型 灵长类动物； （3）通过最终用户的迭代社会行为研究为技术开发提供信息 RSA中的种群。重要的是，拟议的工作将利用早期计划中的成就 在开发植入物平台并将在以下关键方面以这项工作为基础：长期交付 （长达6个月）多个ARV以及将RSA的最终用户可接受性数据纳入目标 产品配置文件。我们的研究策略是由里程碑驱动的，具有明显的预期可交付成果指导进度 产品开发以与未来的临床翻译保持一致。