Challenging and Expanding Paradigms of Aging with HIV

描述(由申请人提供)：本申请的总体目标是支持研究人员的教育和研究工作，他们打算发展自己的职业生涯，成为观察流行病学研究的独立调查员，重点关注艾滋病毒感染者的年龄相关并存(即心肌梗死[MI]、终末期肾病[ESRD]和非艾滋病相关癌症[癌症])。到目前为止，这位候选人已经在艾滋病毒和流行病学方法方面接受了出色的博士培训；她已经开始将研究重点放在艾滋病毒感染老年个体的共病上。职业发展奖允许接受五年的教学和科学培训，通过以下机制建立独立研究调查员的职业生涯：1)通过每周会议、半年度目标评估和使用文件共享软件的生产率跟踪，在研究问题生成、研究设计、统计分析、结果解释、科学交流和艾滋病毒流行病学家斯蒂芬·甘格博士(导师)的科学交流和手稿准备以及与艾滋病毒专家临床医生和研究员凯利·格博博士(共同导师)的老龄化方面提供直接指导；2)咨询退伍军人老龄化队列研究(Vacs)首席研究员、艾滋病毒临床医生和流行病学家老龄化专家艾米·贾斯蒂斯博士，北美艾滋病队列研究协作(NA-ACCORD)首席研究员兼艾滋病毒临床医生和研究员理查德·摩尔博士，以及老年病学家和老年人多病研究带头人辛西娅·博伊德博士；3)在约翰霍普金斯大学彭博公共卫生学院(JHSPH)获得关于老龄化流行病学、疾病过程中衰老的机制和因果推断方法的正式指导；4)在Vacs和NA-ACCORD研究的丰富数据环境中实施拟议的研究；4)利用流行病学统计(STATEPI)研究小组、JHSPH流行病学系和约翰·霍普金斯大学医学院(JHSOM)的丰富资源环境。近期、短期和长期的职业目标包括提高生产力，每年至少出版五份出版物和在科学会议上做一次口头陈述，在2016年前成功争取到R01资金，用于调查老年艾滋病毒感染者多发病的研究，以及分别作为一名富有成效的独立研究调查员实现职业生涯。 据估计，2015年美国艾滋病毒携带者中有50%的人年龄将达到50岁。这项拟议研究的总体目标是通过调查三个具有临床和公共卫生意义的问题来挑战和扩展艾滋病毒老龄化研究的范式：1)艾滋病毒感染者与社会人口学上相似的未感染艾滋病毒的人相比，是否有更高的共病风险？2)传统的或与艾滋病毒相关的风险因素是否会增加艾滋病毒感染者的共病风险？3)开始高效抗逆转录病毒疗法(HAART)的时机对合并疾病的风险有什么影响？这些问题将通过调查以下目标来提出：目标1：评估美国艾滋病病毒感染者和类似未感染者在临床护理中的共病风险差异，按诊断为共病的年龄。目的2：确定美国和加拿大临床护理中HIV感染者共病的传统危险因素和HIV相关危险因素的归因比例。目的3：通过美国和加拿大临床护理中HIV感染者在HAART启动时的CD4计数来确定HAART启动后首次共病事件的风险。 老兵老龄化队列研究(VAS)是一项对10万名艾滋病毒感染者和类似未感染者的纵向、多点观察研究，目的是评估艾滋病毒感染者的年龄相关合并症，使其成为研究目标1的理想队列。尽管这一以男性为主的队列研究结果的普遍性可能受到限制，但艾滋病毒感染者和未感染者在年龄、种族和民族、性别和地理位置方面是匹配的，确保了调查艾滋病毒影响的强大内部有效性。NA-ACCORD是一项针对HIV感染者的纵向、多点观察性研究，招募了115,000名HIV感染者，他们正在努力收集MI、ESRD和癌症事件的数据。这一群体合作的独特定位是解决目标2和目标3，样本量足够大，足以捕捉足够数量的并存事件。1)VISA和NA-ACCORD的数据丰富的环境，2)STATEPI、流行病学系和JHSOM的资源丰富的环境，以及3)由导师和顾问组成的多学科团队允许对这些目标进行调查，这些目标挑战并扩展了现有的艾滋病毒老龄化范式，作为候选人作为独立研究调查员的成功职业生涯的基础。

DESCRIPTION (provided by applicant): The overall goal of this application is to support the education and research endeavors of the investigator, who has the intention of developing a career as an independent investigator of observational epidemiologic research focused on age-related comorbidities (i.e. myocardial infarction [MI], end-stage renal disease [ESRD] and non-AIDS related cancers [cancer]) in HIV-infected individuals. To-date, the candidate has received excellent doctoral training in HIV and epidemiologic methods; she has begun focusing research interests on comorbidities among individuals aging with HIV infection. The career development award allows for five years of didactic and scientific training to establish a career as an independent research investigator via the following mechanisms:1) direct mentorship in research question generation, study design, statistical analysis, interpretation of findings, scientific communication and manuscript preparation from expert HIV epidemiologist Dr. Stephen Gange (mentor) and aging with HIV expert clinician and researcher Dr. Kelly Gebo (co-mentor) through weekly meetings, semi-annual goals evaluation, and productivity tracking using document sharing software; 2) consultation from Dr. Amy Justice, Principal Investigator (PI) of the Veterans Aging Cohort Study (VACS) and expert in aging with HIV clinician and epidemiologist, Dr. Richard Moore, PI of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and expert HIV clinician and researcher, and Dr. Cynthia Boyd, gerontologist and leader in research of multimorbidity in older adults; 3) obtaining formal instruction in aging epidemiology, the mechanism of aging in disease processes and causal inference methods at the Johns Hopkins Bloomberg School of Public Health (JHSPH); 4) implementing the proposed research in the data-rich environment of VACS and NA-ACCORD studies; 4) utilizing the resource-rich environments of the Statistics in Epidemiology (STATEPI) research group, and the Department of Epidemiology, JHSPH, and the Johns Hopkins School of Medicine (JHSOM). Immediate, short-term and longer-term career goals include increasing productivity to at least five publications and one oral presentation at a scientific conference each calendar year, successfully competing for R01 funding for studies investigating multimorbidity in aging HIV-infected individuals by 2016, and achieving a productive career as an independent research investigator, respectively. It is estimated =50% of people living with HIV in the US in 2015 will be aged =50 years. The overall aim of the proposed research is to challenge and expand upon paradigms in aging with HIV research by investigating three questions of clinical and public health significance: 1) Do HIV-infected individuals have a higher risk of comorbidities compared to sociodemographically similar HIV-uninfected individuals? 2) Are traditional or HIV- related risk factors driving the increased risk of comorbidities in HIV-infected individuals? 3) What is the impact of the timing of highly active antiretroviral therapy (HAART) initiation on the risk of comorbidities? These questions will be asked by investigating the following aims: Aim 1: To estimate the difference in risk of comorbidities in HIV-infected and similar -uninfected individuals in the US in clinical care, by age at comorbidity diagnosis. Aim 2: To determine the attributable fraction of traditional and HIV-related risk factors on comorbidities in HIV-infected individuals in clinical care in the US and Canada. Aim 3: To determine the risk of first comorbid event after HAART initiation by CD4 count at HAART initiation in HIV-infected individuals in clinical care in the US and Canada. The Veteran's Aging Cohort Study (VACS) is a longitudinal, multisite observational study of >100,000 HIV- infected and similar -uninfected patients with the aim of evaluating age-related comorbidites in HIV-infected individuals, making it an ideal cohort to investigate Aim 1. Although the generalizability of the findings from this predominantly male cohort may be restricted, the HIV-infected and -uninfected individuals were matched by age, race and ethnicity, sex and geographical location, ensuring strong internal validity to investigate the HIV effect. The NA-ACCORD is a longitudinal, multisite observational study of HIV-infected individuals, enrolling >115,000 HIV-infected participants with data collection efforts underway for MI, ESRD, and cancer events. This collaboration of cohorts is uniquely positioned to address Aims 2 and 3 with a sample size large enough to capture an adequate number of comorbid events. The 1) data-rich environments of the VACS and the NA- ACCORD, 2) resource-rich environments of STATEPI, the Department of Epidemiology and the JHSOM, and 3) assembled multidisciplinary team of mentors and consultants allows for the investigation of these aims, that challenge and expand upon current paradigms in aging with HIV, to serve as the candidate's foundation for a successful career as an independent research investigator.