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

描述（由申请人提供）：该拟定的5年开发期将用于研究和培训活动，以使Steven Y.洪的技能，成为一个 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独立研究员，在资源有限的环境中开展艾滋病毒临床和转化研究; 2）探索在资源有限的环境中优化艾滋病毒感染者的护理，特别强调改善抗逆转录病毒疗法（ART）的提供。他的短期目标是开发一种可持续的模式，用于追踪那些因护理而迷失的ART患者，这种模式可以应用于资源有限的环境中，以尽量减少艾滋病毒耐药性的出现，并优化患者的治疗效果。该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）和卫生系统研究专家的研究指导。培训将侧重于：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其对生物医学研究和早期研究人员职业发展的坚定承诺而闻名。沿着塔夫茨大学地理信息系统中心，该机构是拟议培训活动的理想环境。该候选人组建了一支由具有各种相关专业知识的杰出导师组成的团队，为他的职业发展提供指导：国际艾滋病毒临床研究领域的克莉丝汀·万科博士、资源有限环境中ART项目优化领域的迈克尔·乔丹博士、生物统计学领域的诺玛·特林博士、地理信息系统领域的帕特里克·弗洛伦斯博士和卫生系统研究领域的菲利普·奥东科尔博士。临床研究将在纳米比亚进行，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。失访（LTFU）是目前在资源有限的环境中实现ART治疗成功的最大障碍之一，在开始ART后的前6个月内，平均21%的患者被归类为LTFU，12个月时高达25%。因此，采取干预措施减少ART项目的流失至关重要。违约者追踪是在这些环境中使用的一种常用方法，用于联系和链接中断护理或治疗的患者重新接受护理并减少LTFU。优化违约者追踪方法可能是一个关键的未开发的最小资源干预，可能会导致高产量的结果。加强对每日追踪的违约者追踪，目标是在患者未服药的48小时内将患者重新联系到护理中，这有可能减少LTFU并显着改善ART治疗结果。该项目旨在确定加强追踪纳米比亚接受抗逆转录病毒治疗的患者的有效性，这些患者已经失去了对日常追踪的照顾，以降低长期随访率并改善患者结局（人群抗逆转录病毒治疗依从性、病毒学抑制和死亡率）。首先，将在400例患者的初步追踪研究中确定LTFU的预测因素和原因。使用这些数据设计和优化干预措施，将在纳米比亚8个患者追踪强化中心与8个标准治疗中心（共3，200例患者）进行一项群集随机对照试验，比较拟定结局。该项目的具体目的如下：（1）确定LTFU的预测因素和原因;（2）确定患者追踪强化在降低LTFU发生率方面的有效性（主要结局），与标准治疗违约者追踪相比;以及（3）确定患者追踪强化在改善临床和病毒学结局方面的有效性（次要结局），与标准治疗违约者追踪相比。这项研究有可能确定一个最低限度的资源战略，可以在整个纳米比亚和其他资源有限的环境中应用，以应对患者保留的挑战，从而降低全球数百万ART患者的发病率和死亡率。 公共卫生相关性：在资源有限的情况下，接受抗逆转录病毒治疗（ART）的患者失访率很高，可能导致出现艾滋病毒耐药性、治疗失败和死亡。该项目将评估LTFU的预测因素和原因，并确定加强追踪纳米比亚已失去护理的ART患者的有效性，以降低LTFU率并改善患者结局。这项研究是相关的，因为它有可能确定一个最低限度的资源战略，可以在整个纳米比亚和其他资源有限的环境中应用，以减少长期使用，从而降低发病率和死亡率在资源有限的环境中接受抗逆转录病毒治疗的大量人口。

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.