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: 10327146
• 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/10327146
• 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; Childhood; 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; 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; 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; 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; virology

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 艾滋病毒携带者和坚持斗争的青年将受益于长效抗逆转录病毒药物(LAARV)，不久将是 在美国提供，比其他组更多。13岁至29岁的艾滋病毒携带者较少 参与艾滋病毒护理级联的所有步骤，导致与艾滋病毒相关的健康差距被夸大， 这组患者的总体病毒抑制率较低。耻辱、心理健康问题、认知缺陷和 行政职能，以及多种社会健康决定因素中的障碍可能会阻碍 年轻人能够坚持抗逆转录病毒并为自己获得这项技术的好处，他们的 家庭，以及他们的社交网络和社区。这个项目的主要目标是，嵌套在资助的 国际母婴青少年艾滋病临床试验小组(IMPAACT)2022年，正在开发一种 独立的学术研究方案，解决在青年中优化使用LAARV的问题， 最终目标是设计切实可行的干预措施，以最大限度地提高其效益。这四年的培训和研究 计划将包括：1)使用新的方法了解生物、心理、社会和认知的作用 LAARV成功的因素和潜在地建立LAARV疗效的预测因子 青年使用前的特点；2)开发和试验新的生物测定方法，以便能够在实地收集 用于临床试验或AS的干血斑(DBS)或干血浆萃取器(DPE)LAARV测量 接受LAARV治疗的YLHIV患者的治疗药物监测；3)学习和利用人群PK 了解LAARV上YHIV病毒PK变异性来源的建模方法。培训将包括 正式的课程、直接的指导和基于实践的指导经验，以及 生物统计学、认知神经科学、定量药理学和化验发展 群体药代动力学。通过从她的导师和合作者那里获得所有这些方法的培训，她说。 Weld将成为一名临床医生--长效传染病疗法的研究人员 评估新的交付策略和技术的出现，并有能力改变她所在的领域。 在授权期内进行的调查结果将为随后的 设计干预研究，通过较少频繁的给药策略改善年轻人的艾滋病毒相关结局， 并提交进一步的资金建议，以支持这一调查。