Novel Measures and Theory of Pediatric Antiretroviral Therapy Adherence in Uganda

描述(由申请人提供)：在资源有限的环境中感染艾滋病毒的儿童不能可靠地达到在萨那环境下成人接受抗逆转录病毒疗法(ART)的高水平，因此是研究的优先人群。儿童的艺术依从性评估由于自我报告的局限性和缺乏可行的客观措施而变得复杂。此外，现有的遵守措施没有检测到遵守失误，并在病毒学失败之前提供了改善遵守的机会。在资源有限的情况下，需要新的依从性监测策略来更好地理解和干预儿科抗逆转录病毒药物的依从性。在这个为期五年的K23职业发展奖申请中，我建议获得解决这些问题所需的技能，并实现我的长期职业目标，即在资源有限的情况下提高儿科ART的依从性和治疗结果。通过之前在中国克林顿基金会的工作，我对儿科艾滋病毒/艾滋病的治疗和护理有了很好的了解。我还拥有卫生服务研究的硕士学位，是正在进行的一项关于乌干达儿童抗逆转录病毒治疗依从性的多项措施的R21研究的首席研究员。然而，我需要更好地理解依从性测量的量化分析，新的依从性测量，儿童发展和心理健康，以及混合方法分析，以开发和测试新的行为干预措施，以提高儿科ART依从性。我已确定大卫·邦斯伯格博士为我的主要导师。他是一位坚持研究的国际专家，在指导方面有着出色的记录。朱利叶斯·基瓦努卡博士和史蒂夫·萨夫伦博士将分别在儿科艾滋病毒/艾滋病治疗和护理以及行为科学领域担任共同导师。利用这些技能，我建议1)在乌干达5岁以下艾滋病毒感染儿童的照顾者中检查基于无线技术的新型坚持措施的表现；2)对这些新型坚持措施的可行性和可接受性进行混合方法评估；3)在资源有限的情况下，建立基于社会资本的幼儿坚持行为的理论模型。这种模式可能适合幼儿，因为他们的坚持在很大程度上反映了照顾者的行为。拟议的培训和指导将为我提供成为一名成功的独立研究人员所需的技能和经验。在获奖期接近尾声时，我将提交一份投资回报申请，以测试基于无线技术和理论模型的干预措施，该干预措施可能会改善感染艾滋病毒的乌干达儿童的依从性和病毒抑制。公共卫生相关性：良好的依从性对于实现和维持抗逆转录病毒疗法的临床益处以及预防病毒学失败和耐药性至关重要。在资源有限的情况下，儿科ART的依从性是次要的，治疗仅限于一线方案。拟议的研究可以显著提高依从性，从而改善健康并延长一线治疗的使用时间。此外，通过将昂贵的病毒学测试限制在坚持失败的个人身上，它可以改善受限资源的分配。

DESCRIPTION (provided by applicant): HIV-infected children in resource-limited settings do not reliably achieve the high levels of adherence to antiretroviral therapy (ART) seen in adults in the sanne setting and therefore represent a priority population for research. ART adherence assessment in children is complicated by limitations in self-report and absence of feasible objective measures. Moreover, existing adherence measures do not detect adherence lapses and offer opportunities to improve adherence before virologic failure. Novel adherence monitoring strategies are needed to better understand and intervene on pediatric ART adherence in resource-limited settings. In this five-year K23 career development award application, I propose to acquire the skills needed to address these issues and to achieve my long-term career goal of improving pediatric ART adherence and treatment outcomes in resource-limited settings. I have a good understanding of pediatric HIV/AIDS treatment and care through my prior work with the Clinton Foundation in China. I also have a master's degree in Health Services Research and am the principal investigator of an ongoing R21 study of multiple measures of ART adherence in Ugandan children. I, however, need a better understanding of quantitative analysis for adherence measures, novel adherence measurements, child development and mental health, and mixed- methods analysis to develop and test novel behavioral intervenfions to improve pediatric ART adherence. I have identified Dr. David Bangsberg as my primary mentor. He is an international expert in adherence research and has an outstanding track record of mentorship. Dr. Julius Kiwanuka and Dr. Steve Safren will serve as co-mentors in the areas of pediatric HIV/AIDS treatment and care and behavioral science, respectively. Using these skills, I propose to 1) examine the performance of novel adherence measures based on wireless technology among caregivers of HIV-infected children under age five in Uganda; 2) perform mixed method assessments of the feasibility and acceptability of these novel adherence measures; and 3) develop a theoretic model for ART adherence behavior based on social capital for young children in a resource-limited setting. This model may be appropriate for young children, because their adherence largely reflects the behavior of their caregivers. The proposed training and mentorship will provide me with the skills and experience necessary to become a successful independent researcher. Toward the end of the award period, I will submit an ROI application to test an intervention based on wireless technology and the theoretic model that may improve adherence and viral suppression among HIV-infected Ugandan children. PUBLIC HEALTH RELEVANCE: Excellent adherence is essential for achieving and maintaining the clinical benefits of ART and for preventing virologic failure and drug resistance. Pediatric ART adherence in resource-limited settings is suboptimal and treatment is limited to a first-line regimen. The proposed research could significantly improve adherence, thus improving health and prolonging the use of first-line therapy. Moreover, it could improve the allocation of constrained resources by limiting expensive virologic testing to individuals with adherence failures.