Preventing Weight Gain and Diabetes in People with HIV in South Africa

项目摘要 背景：肥胖和糖尿病是HIV感染者发病率和死亡率的重要危险因素 (PWH)，特别是在撒哈拉以南非洲，那里的卫生系统已经在努力应对艾滋病毒/艾滋病的迅速上升。 代谢性疾病基于Dolutegravir（DTG）的抗逆转录病毒疗法（ART）最近已被采用为 尽管有证据表明这与体重过度增加有关，但该区域大部分地区的一线治疗方案仍然存在。而 艾滋病毒护理系统提供了一个有能力的卫生系统平台，肥胖和糖尿病预防不是当前的重点。 护理模式的重点。候选人：我是马萨诸塞州总医院传染病科的临床研究员 医院和一名在全球卫生流行病学方面接受过博士级培训的医生兼科学家， 发表的观察性研究记录。然而，我最近照顾威尔斯亲王医院的经历， 希望获得设计和执行干预性试验的新技能，以预防代谢性疾病， 人口我的首要职业目标是成为一名独立的，NIH资助的医生科学家， 在治疗艾滋病毒的代谢并发症，并在开发和测试临床干预， 避免这些并发症。培训：为了实现研究独立性，我将需要额外的培训， 1)肥胖医学和糖尿病预防，2）基于行为模型的干预设计，以及3） 开展和分析预防艾滋病毒代谢并发症的临床试验。导师：我的训练和 研究计划将由我的主要导师Mark Siedner博士监督，他有广泛的指导 经验丰富，并在南非进行观察性队列研究和临床试验。卢嘉仪医生 （肥胖医学和糖尿病预防），Christina Psaros（基于行为模型的干预设计）， 和Deborah Wexler（临床试验的进行和分析）将担任共同导师，提供额外的 专注的专业知识。我还将收到我的科学顾问委员会的年度反馈，其中包括博士。 罗谢尔·瓦伦斯基，内奥米·莱维特，罗伯特·帕克和蒂尔·贝尼豪森。研究：在我的指导下 我将在南非的PWH中探索DTG的代谢影响，并开发和试点 通过三个具体目标来减轻这些并发症的干预：1）确定行为 南非PWH过渡到基于DTG的ART的体重变化和葡萄糖耐受不良的相关性; 2)制定一种可接受的和适当的干预措施，以防止体重增加和糖尿病， 威尔斯亲王医院在南非进行以DTG为基础的抗逆转录病毒疗法;及3）进行一项因素随机可行性研究， 干预措施，以防止体重增加和糖尿病的PWH之间的DTG为基础的ART与常规护理。我们将 通过与威康信托基金资助的非洲健康研究现有合作开展这项研究 研究所（AHRI）。通过这段时间的培训和研究，我将很好地实现研究 独立性，并计划在该项目的第四年提交NIH R 01申请，以测试 一项预防南非PWH患者体重增加和糖尿病的干预措施。

PROJECT SUMMARY Background: Obesity and diabetes are important risk factors for morbidity and mortality in people with HIV (PWH), especially in sub-Saharan Africa where health systems are already grappling with a rapid rise in metabolic disease. Dolutegravir (DTG)-based antiretroviral therapy (ART) has recently been adopted as the first-line regimen in most of the region, despite evidence that it is associated with excess weight gain. While the HIV care system offers a capable health systems platform, obesity and diabetes prevention is not a current focus of care paradigms. Candidate: I am a Clinical Fellow in Infectious Diseases at Massachusetts General Hospital and a physician-scientist with doctoral-level training in global health epidemiology and a strong track record of published observational research. However, my recent experiences caring for PWH have led to a desire to gain new skills in the design and execution of interventional trials to prevent metabolic disease in this population. My overarching career goal is to become an independent, NIH-funded physician-scientist with expertise in the metabolic complications of treated HIV, and in developing and testing clinical interventions to prevent these complications. Training: To achieve research independence, I will require additional training in 1) obesity medicine and diabetes prevention, 2) behavioral model-based intervention design, and 3) the conduct and analysis of clinical trials to prevent metabolic complications of HIV. Mentors: My training and research plans will be overseen by my primary mentor Dr. Mark Siedner, who has extensive mentoring experience and conducts both observational cohort studies and clinical trials in South Africa. Drs. Janet Lo (obesity medicine and diabetes prevention), Christina Psaros (behavioral model-based intervention design), and Deborah Wexler (the conduct and analysis of clinical trials) will serve as co-mentors to provide additional focused expertise. I will also receive annual feedback from my Scientific Advisory Board, which includes Drs. Rochelle Walensky, Naomi Levitt, Robert Parker, and Till Bärnighausen. Research: With guidance from my team of mentors, I will explore the metabolic effects of DTG among PWH in South Africa and develop and pilot an intervention to mitigate these complications through three specific aims: 1) To determine the behavioral correlates of weight change and glucose intolerance for PWH transitioning to DTG-based ART in South Africa; 2) To develop an acceptable and contextually appropriate intervention to prevent weight gain and diabetes in PWH on DTG-based ART in South Africa; and 3) To conduct a factorial-randomized feasibility study of interventions to prevent weight gain and diabetes among PWH on DTG-based ART versus usual care. We will carry out this research through existing collaborations with the Wellcome Trust-funded Africa Health Research Institute (AHRI). Through this period of training and research, I will be well positioned to achieve research independence and plan to submit an NIH R01 application in the fourth year of this project to test the efficacy of an intervention to prevent weight gain and diabetes in PWH in South Africa.