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者的教育和研究工作，研究者有意发展作为观察性流行病学研究的独立研究者的职业生涯，该研究重点关注HIV感染者中与年龄相关的合并症（即心肌梗死[MI]、终末期肾病[ESRD]和非AIDS相关癌症[癌症]）。迄今为止，候选人已经接受了艾滋病毒和流行病学方法的优秀博士培训;她已经开始关注艾滋病毒感染者中老年人的合并症的研究兴趣。职业发展奖允许通过以下机制进行五年的教学和科学培训，以建立作为独立研究调查员的职业生涯：1）在研究问题生成、研究设计、统计分析、结果解释、科学交流和手稿准备方面直接指导艾滋病毒流行病学专家Stephen Gange博士（导师），并与艾滋病毒专家临床医生和研究员Kelly Gebo博士一起老化通过每周会议、半年度目标评估和使用文件共享软件的生产率跟踪（共同指导）; 2）退伍军人老龄化队列研究（VACS）的主要研究者（PI）、老龄化专家Amy Justice博士与艾滋病临床医生和流行病学家Richard摩尔博士（北美艾滋病队列研究与设计合作组织PI）的咨询（NA-ACCORD）和艾滋病毒专家临床医生和研究人员，以及老年病学家和老年人多发病研究领导人Cynthia Boyd博士; 3）在约翰霍普金斯彭博公共卫生学院（JHSPH）获得关于衰老流行病学、疾病过程中衰老机制和因果推理方法的正式指导; 4）在VACS和NA-ACCORD研究的数据丰富的环境中实施拟议的研究; 4）利用流行病学统计（STATEPI）研究小组、流行病学系、JHSPH和约翰霍普金斯医学院（JHSOM）资源丰富的环境。近期，短期和长期的职业目标包括提高生产力，至少五个出版物和一个口头报告在科学会议上每个日历年，成功地竞争R 01资金的研究调查在老龄艾滋病毒感染者的多morphine到2016年，并实现一个富有成效的职业生涯作为一个独立的研究调查员，分别。 据估计，到2015年，美国50%的HIV感染者年龄在50岁以上。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化研究的范式：1）与社会人口统计学上相似的艾滋病毒未感染者相比，艾滋病毒感染者是否有更高的合并症风险？2)传统的或HIV相关的危险因素是否导致HIV感染者合并症的风险增加？3)高效抗逆转录病毒治疗（HAART）开始的时间对合并症的风险有什么影响？这些问题将通过调查以下目的来提出：目的1：根据合并症诊断时的年龄，估计美国临床护理中HIV感染者和类似未感染者合并症风险的差异。目标二：确定美国和加拿大临床护理中HIV感染者合并症的传统和HIV相关风险因素的可归因比例。目标3：在美国和加拿大的临床护理中，通过HAART启动时的CD 4计数确定HIV感染者在HAART启动后发生首起共病事件的风险。 退伍军人衰老队列研究（VACS）是一项纵向、多中心观察性研究，纳入了> 100，000例HIV感染和类似未感染患者，目的是评估HIV感染个体中与年龄相关的合并症，使其成为研究目标1的理想队列。虽然从这个主要是男性队列的结果的普遍性可能受到限制，艾滋病毒感染和未感染的个人的年龄，种族和民族，性别和地理位置相匹配，确保强有力的内部效度调查艾滋病毒的影响。NA-ACCORD是一项对HIV感染者进行的纵向、多中心观察性研究，招募了> 115，000名HIV感染者，正在收集MI、ESRD和癌症事件的数据。队列的这种合作具有独特的优势，能够实现目标2和3，样本量足够大，能够采集足够数量的共病事件。1）VACS和雅阁的数据丰富的环境，2）STATEPI，流行病学系和JHSOM的资源丰富的环境，以及3）组装的多学科导师和顾问团队允许调查这些目标，挑战和扩展当前的艾滋病毒老化范例，作为候选人作为独立研究调查员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.