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在抗逆转录病毒治疗（ART）方面的依从性并不像在桑尼环境中成人那样高，因此是研究的重点人群。由于自我报告的局限性和缺乏可行的客观措施，儿童抗逆转录病毒治疗依从性评估变得复杂。此外，现有的依从性措施不能检测到依从性失误，并提供机会在病毒学失败之前改善依从性。需要新的依从性监测策略来更好地了解和干预资源有限环境下的儿科抗逆转录病毒治疗依从性。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抗逆转录病毒治疗的依从性和治疗效果。通过在中国克林顿基金会的工作，我对儿童艾滋病的治疗和护理有很好的了解。我还拥有卫生服务研究硕士学位，是一项正在进行的R21研究的首席研究员，该研究是关于乌干达儿童抗逆转录病毒治疗依从性的多种措施。然而，我需要更好地理解依从性措施的定量分析，新型依从性测量，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，以提高儿童抗逆转录病毒治疗的依从性。我指定大卫·班斯伯格博士为我的主要导师。他是依从性研究方面的国际专家，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·萨夫伦博士将分别担任儿科艾滋病毒/艾滋病治疗和护理以及行为科学领域的共同导师。利用这些技能，我建议：1)检查基于无线技术的新型依从性措施在乌干达5岁以下艾滋病毒感染儿童护理人员中的表现；2)对这些新型依从性措施的可行性和可接受性进行混合方法评估；3)在资源有限的环境下，建立基于社会资本的幼儿抗逆转录病毒治疗依从性行为理论模型。这种模式可能适用于幼儿，因为他们的依从性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员所需的技能和经验。在奖励期结束时，我将提交一份ROI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治疗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，儿童抗逆转录病毒治疗的依从性是次优的，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，它可以通过将昂贵的病毒学检测限制在依从性失败的个体上来改善有限资源的分配。

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.