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，研究者有意成为一名独立的观察性流行病学研究研究者，专注于hiv感染者中与年龄相关的合并症（如心肌梗死[MI]，终末期肾病[ESRD]和非艾滋病相关癌症[癌症]）。迄今为止，该候选人在艾滋病毒和流行病学方法方面接受了优秀的博士培训；她已经开始将研究兴趣集中在艾滋病毒感染老年人的合并症上。职业发展奖允许通过以下机制进行5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，HIV流行病专家Stephen Gange博士（导师）与HIV专家临床医生和研究员Kelly Gebo博士（联合导师）通过每周会议、半年度目标评估和使用文档共享软件跟踪生产力进行科学交流和文稿编写；2)咨询美国退伍军人老龄化队列研究（VACS）首席研究员、艾滋病临床和流行病专家Amy Justice博士、北美艾滋病队列研究与设计合作（NA-ACCORD）首席研究员、艾滋病临床和研究专家Richard Moore博士、老年病学专家、老年人多病研究负责人Cynthia Boyd博士；3)在约翰霍普金斯大学彭博公共卫生学院（JHSPH）获得衰老流行病学、衰老在疾病过程中的机制和因果推理方法的正式指导；4)在VACS和NA-ACCORD研究数据丰富的环境下实施所提出的研究；4)利用流行病学统计（STATEPI）研究组、JHSPH流行病学系和约翰霍普金斯医学院（JHSOM）的资源丰富的环境。近期、短期和长期的职业目标包括提高生产力，每年至少发表五篇论文，在一次科学会议上做一次口头报告，到2016年成功争取到R01基金，用于调查老年艾滋病毒感染者的多发病情况，并分别成为一名独立研究调查员。

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.