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，艾滋病毒感染儿童不能可靠地达到桑内环境中成人抗逆转录病毒治疗（ART）的高依从性，因此代表了研究的优先人群。自我报告的局限性和缺乏可行的客观措施使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依从性失误，并提供机会，以提高病毒学失败之前的依从性。需要新的依从性监测策略，以更好地了解和干预资源有限的环境中儿科ART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，并实现我在资源有限的环境中改善儿科ART依从性和治疗结果的长期职业目标。通过我之前在克林顿基金会在中国的工作，我对儿科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硕士学位，并且是正在进行的R21研究的主要研究员，该研究旨在对乌干达儿童的ART依从性进行多种测量。然而，我需要更好地理解依从性测量的定量分析，新的依从性测量，儿童发育和心理健康，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。我已经确定大卫邦斯伯格博士为我的主要导师。他是坚持研究的国际专家，并有出色的指导记录。Julius Kiwanuka博士和Steve Safren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。使用这些技能，我建议1）检查性能的新的坚持措施之间的照顾者的艾滋病毒感染的儿童在乌干达的5岁以下的无线技术的基础上; 2）执行混合方法评估的可行性和可接受性，这些新的坚持措施;和3）开发一个理论模型的基础上，社会资本的幼儿在资源有限的设置ART坚持行为。这种模式可能适合幼儿，因为他们的依从性在很大程度上反映了他们的照顾者的行为。拟议的培训和指导将为我提供必要的技能和经验，成为一个成功的独立研究员。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艾滋病毒感染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ART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，儿科抗逆转录病毒疗法的依从性是次优的，治疗仅限于一线方案。拟议的研究可以显着提高依从性，从而改善健康并延长一线治疗的使用。此外，它可以通过限制对依从性失败的个体进行昂贵的病毒学测试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.