Namibia ART Patient Tracing Intensification and Predictors of Loss to Follow-up

描述(由申请人提供)：这一拟议的5年发展期将用于研究和培训活动，使史蒂芬·Y·洪博士具备成为 独立调查员。洪博士的长期职业目标是：1)成为塔夫茨大学医学院的一名独立研究员，在资源有限的情况下从事艾滋病毒临床和转化研究；2)探索在资源有限的情况下优化对艾滋病毒感染患者的护理，特别强调改善抗逆转录病毒治疗(ART)的提供。他的短期目标是开发一种可持续的模式，追踪因护理而走失的抗逆转录病毒患者，这种模式可以应用于资源有限的环境，以最大限度地减少艾滋病毒耐药性的出现，并优化患者的预后。培训将包括正式的课堂学习、研究项目，以及来自国际艾滋病毒临床研究、ART计划优化、流行病学、生物统计学、地理信息系统(GIS)和卫生系统研究的专家的研究指导。培训的重点是：1)专门的流行病学方法；2)数据管理和统计分析；3)地理信息系统技术。塔夫茨医学中心的地理医学和传染病部门以及塔夫茨临床和转化科学研究所以致力于生物医学研究和早期研究人员的职业发展而闻名。与塔夫茨大学的地理信息系统中心一起，该机构是拟议中的培训活动的理想环境。这位候选人已经组建了一支具有各种相关专业知识的杰出导师团队，为他的职业发展提供指导：Christine Wanke博士在国际HIV临床研究方面，Michael Jordan博士在资源有限的环境下进行ART项目优化，Norma Terrin博士在生物统计学领域，Patrick Florance博士在GIS领域，Philip Odonkor博士在卫生系统研究领域。临床研究将在纳米比亚与纳米比亚大学医学院和纳米比亚卫生和社会服务部合作进行。失访(LTFU)目前是在资源有限的情况下实现ART治疗成功的最大障碍之一，在开始ART后的前六个月，平均有21%的患者被归类为LTFU，而在12个月时这一比例高达25%。因此，减少抗逆转录病毒治疗计划中的人员流失的干预措施至关重要。违约者追踪是在这些环境中使用的一种常见方法，用于联系中断护理或治疗的患者，并将其重新纳入护理并减少LTFU。优化违约者追踪的方法可能是一种严重未开发的最小资源干预，可能导致高收益结果。加强对每日Tracin的违约者追踪，目标是在患者没有药物治疗后48小时内将患者联系到护理中，这可能会减少LTFU并显著改善ART治疗结果。该项目旨在确定在纳米比亚加强对失去日常护理的抗逆转录病毒治疗患者的追踪的有效性，以降低LTFU发生率并改善患者结果(人群抗逆转录病毒疗法的依从性、病毒学抑制和死亡率)。首先，将在一项对400名患者进行的试验性追踪研究中确定LTFU的预测因素和原因。利用这些数据来设计和优化干预措施，将在纳米比亚进行一项整群随机对照试验，将8个患者追踪强化点与8个标准护理点(总共3200名患者)进行比较，以确定拟议的结果。该项目的具体目标如下：(1)确定LTFU的预测因素和原因；(2)确定与标准护理违规者追踪相比，患者追踪强化在降低LTFU(主要结果)率方面的有效性；以及(3)与标准护理违规者追踪相比，确定患者追踪强化在改善临床和病毒学结果(次要结果)方面的有效性。这项研究有可能确定一种可以在纳米比亚和其他资源有限的环境中应用的最小资源战略，以应对留住患者的挑战，从而降低全球数百万接受抗逆转录病毒治疗的人的发病率和死亡率。 公共卫生相关性：在资源有限的情况下，接受抗逆转录病毒疗法(ART)的患者的高随访率(LTFU)可能导致艾滋病毒耐药性的出现、治疗失败和死亡。该项目将评估LTFU的预测因素和原因，并确定加强对纳米比亚失去护理的ART患者的追踪的有效性，以降低LTFU的发生率并改善患者的预后。这项研究之所以有意义，是因为它有可能确定一种可以在纳米比亚和其他资源有限的环境中应用的最小资源战略，以减少LTFU，从而减少在资源有限的环境中接受抗逆转录病毒治疗的大量人的发病率和死亡率。

DESCRIPTION (provided by applicant): This proposed 5-year development period will be used for research and training activities that will give Dr. Steven Y. Hong the skills to become an independent investigator. Dr. Hong's long-term career goals are: 1) to become an independent researcher with a faculty position at Tufts University School of Medicine conducting HIV clinical and translational research in resource-limited settings; and 2) to explore optimization of care of HIV-infected patients in resource-limited settings with a special emphasis on improving the delivery of antiretroviral therapy (ART). His short-term goal is to develop a sustainable model of tracing ART patients who have become lost from care that can be applied in resource-limited settings to minimize the emergence of HIV drug resistance and optimize patient outcomes. This training will include formal class study, a research project, and research mentorship from experts in international HIV clinical research, ART program optimization, epidemiology, biostatistics, geographic information systems (GIS), and health systems research. The training will focus on: 1) specialized epidemiologic methods; 2) data management and statistical analysis; and 3) GIS technology. The Division of Geographic Medicine and Infectious Diseases at Tufts Medical Center and the Tufts Clinical and Translational Science Institute are well known for their strong commitment to biomedical research and career development of early-stage investigators. Along with the GIS Center at Tufts University, this institution is an ideal environment for the proposed training activities. The candidate has assembled a team of outstanding mentors with varied and relevant expertise to provide guidance in his career development: Dr. Christine Wanke in international HIV clinical research, Dr. Michael Jordan in ART program optimization in resource-limited settings, Dr. Norma Terrin in biostatistics, Patrick Florance in GIS, and Dr. Philip Odonkor in health systems research. The clinical research will take place in Namibia, in collaboration with the University of Namibia Medical School and the Namibia Ministry of Health and Social Services. Loss to follow-up (LTFU) is currently one of the largest impediments to achieving ART treatment success in resource-limited settings where an average of 21% of patients are classified as LTFU in the first six months after starting ART, and up to 25% at 12 months. As such, interventions to reduce attrition from ART programs are of the utmost importance. Defaulter tracing is a common method utilized in these settings to contact and link patients who have interrupted care or treatment back into care and decrease LTFU. Optimizing methods for defaulter tracing may be a critically untapped minimal-resource intervention which could lead to high yield results. Intensifying defaulter tracing to daily tracin with the goal of linking patients back into care within 48 hours of a patient being without medication has the potential to reduce LTFU and significantly improve ART treatment outcomes. This project seeks to determine the efficacy of intensifying the tracing of patients on ART in Namibia who have become lost to care to daily tracing, in order to decrease LTFU rates and improve patient outcomes (population ART adherence, virologic suppression, and mortality). First, predictors of and reasons for LTFU will be identified in a pilot tracing study o 400 patients. Using these data to design and optimize the intervention, a cluster randomized controlled trial will be conducted in Namibia of 8 patient tracing intensification sites compared t 8 standard-of-care sites (3,200 total patients) in regards to the proposed outcomes. The Specific Aims of the project are as follows: (1) To identify predictors of and reasons for LTFU; (2) To determine the efficacy of patient tracing intensification in decreasing rates of LTFU (primary outcome), compared to standard- of-care defaulter tracing; and (3) To determine the efficacy of patient tracing intensification in improving clinical and virologic outcomes (secondary outcomes), compared to standard-of-care defaulter tracing. This research has the potential to identify a minimal-resource strategy that can be applied throughout Namibia and other resource-limited settings to address the challenge of patient retention, thus reducing morbidity and mortality in the millions of people on ART globally. PUBLIC HEALTH RELEVANCE: High rates of loss to follow-up (LTFU) of patients on antiretroviral therapy (ART) in resource-limited settings can lead to the emergence of HIV drug resistance, treatment failure, and death. This project will assess predictors of and reasons for LTFU and determine the efficacy of intensifying the tracing of ART patients in Namibia that have become lost to care, in order to decrease LTFU rates and improve patient outcomes. This research is relevant because it has the potential to identify a minimal-resource strategy that can be applied throughout Namibia and other resource-limited settings to decrease LTFU, thus reducing morbidity and mortality in the large number of people receiving ART in resource-limited settings.