Optimizing the Use of Long-Acting Antiretrovirals for Youth Living withHIV

优化长效抗逆转录病毒药物对青少年艾滋病毒感染者的使用

• 批准号: 10487556
• 负责人: Ethel Derby Weld
• 金额: $ 19.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487556
• 关键词: 18 year old; AIDS clinical trial group; AIDS/HIV problem; Address; Adherence; Adolescent; Adult; Age-Years; Anti-Retroviral Agents; Assessment tool; Award; Awareness; Behavior; Behavioral; Biological Assay; Biometry; Blood; Caring; Categories; Characteristics; Clinical; Clinical Pharmacology; Clinical Trials; Clinical Trials Network; Cognition; Cognitive; Cold Chains; Collection; Communicable Diseases; Communities; Data; Decision Making; Development; Dose; Drug Kinetics; Drug Monitoring; Ensure; Family; Foundations; Frequencies; Funding; Goals; HIV; HIV-infected adolescents; Healthcare; Impulsivity; Individual; Injections; International; International Maternal Pediatric Adolescent AIDS Clinical Trials; Intervention; Intervention Studies; Investigation; Knowledge; Lead; Learning; Link; Longevity; Matched Group; Measurement; Measures; Mental Depression; Mental Health; Mental disorders; Mentors; Methodology; Methods; Modeling; Morbidity - disease rate; Oral; Outcome; Participant; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Plasma; Population; Procedures; Property; Quality of life; Questionnaires; Research; Research Personnel; Role; Safety; Social Network; Societies; Source; Spottings; Subgroup; Surveys; Technology; Testing; Therapeutic; Therapeutic Uses; Training; Treatment outcome; Viral; Viral Load result; Welding; Youth; aged; assay development; base; biopsychosocial; brain health; career; clinical care; cognitive neuroscience; design; executive function; experience; health disparity; improved; improved outcome; interest; mortality; neurobehavioral; novel; novel therapeutics; pediatric human immunodeficiency virus; pharmacokinetic model; programs; psychosocial; research clinical testing; skills; social health determinants; social stigma; stem; substance use; success; therapy design; tool; transmission process; treatment as prevention; treatment group; treatment strategy

PROJECT SUMMARY/ ABSTRACT Youth with HIV and adherence struggles stand to benefit from long-acting antiretrovirals (LAARV), soon to be available in the U.S., more than other groups. Youth living with HIV between 13 and 29 years of age are less engaged in all steps of the HIV care cascade, resulting in exaggerated HIV-related disparities in health and an low rates of overall viral suppression in this group. Stigma, mental health issues, deficits in cognition and executive functioning, and obstacles within multiple categories of social determinants of health can hamper youths’ ability to sustain antiretroviral adherence and reap the benefits of this technology for themselves, their families, and their social networks and communities. The primary goal of this project, nested within the funded trial International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) 2022, is to develop an independent scholarly research program addressing the optimization of the use of LAARV in youth, with the ultimate goal of designing practical interventions to maximize their benefit. This four-year training and research program will consist of: 1) employing novel methods to understand the role of biopsychosocial and cognitive factors in the success of LAARV and potentially establish predictors of the efficacy of LAARV based on various pre-use characteristics in youth; 2) developing and piloting novel bioassays to enable in-the-field collections of Dried Blood Spot (DBS) or Dried Plasma Extractor (DPE) LAARV measurements for use in clinical trials or as therapeutic drug monitoring among YLHIV receiving LAARV; and 3) Learning and leveraging population PK modelling approaches to understand the sources of PK variability in YHIV on LAARV. The training will include formal coursework, direct mentoring, and guided practice-based experience with new methodologies in biostatistics, cognitive neuroscience, quantitative pharmacology and assay development, and advanced population pharmacokinetics. By gaining training from her mentors and collaborators in all these methods, Dr. Weld will establish herself as a clinician-researcher in long-acting infectious disease therapeutics equipped to assess new delivery strategies and technologies as they emerge, and capable of transforming her field. Results of the investigations conducted during the award period will establish a foundation for the subsequent design of interventional studies to improve HIV-related outcomes in youth with less-frequent dosing strategies, and submission of further funding proposals to support this line of inquiry.

项目摘要/摘要 艾滋病毒和依从性挣扎的青年将受益于长效抗逆转录病毒（LAARV），很快就会成为 在美国购买，比其他团体更多。患有艾滋病毒13至29岁的艾滋病毒的青年较少 参与了艾滋病毒护理级联的所有步骤，导致与艾滋病毒有关的健康差异和 该组的总体病毒抑制率低。污名，心理健康问题，在认知和 执行功能，以及在健康的多种类别内的障碍可能会妨碍 青年人维持抗逆转录病毒依从性并从中获得这项技术的好处的能力 家庭及其社交网络和社区。该项目的主要目标是嵌套在资助的 试验国际孕产妇青少年艾滋病临床试验小组（Impaact）2022 独立科学研究计划，涉及在青年中使用LAARV的优化， 设计实用干预措施以最大化其收益的最终目标。这项为期四年的培训和研究 程序将包括：1）采用新颖的方法来了解生物心理和认知的作用 LAARV成功的因素以及基于各种LAARV效率的潜在预测指标 青年的预先使用特征； 2）开发和试行新颖的生物测定，以实现现场收藏 干血点（DB）或干血浆提取器（DPE）LAARV测量值用于临床试验或AS 接受LAARV的YLHIV中的治疗药物监测； 3）学习和利用人口PK 建模方法以了解LAARV上YHIV中PK变异性的来源。培训将包括 正式的课程工作，直接心理和基于指导的实践经验，并具有新的方法 生物统计学，认知神经科学，定量药物和测定开发以及先进 人口药代动力学。通过接受所有这些方法的导师和合作者的培训，博士 韦尔德将在提供长期感染性疾病疗法的临床研究者中确立自己 评估新的交付策略和技术出现，并能够改变自己的领域。 奖励期间进行的调查结果将为后续的 介入研究的设计，以改善较少剂量策略的年轻人中与HIV相关的结果， 并提出进一步的资金建议，以支持这一调查。