Challenging and Expanding Paradigms of Aging with HIV

挑战和扩展艾滋病毒老龄化范式

• 批准号: 8518226
• 负责人: Keri Nicole Althoff
• 金额: $ 12.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-08 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518226
• 关键词: Acquired Immunodeficiency Syndrome; Address; Age; Age-Years; Aging; American; Anti-Retroviral Agents; Area; Automobile Driving; Biological; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Calendar; Canada; Cells; Cessation of life; Characteristics; Clinical; Clinical Practice Guideline; Cohort Studies; Collaborations; Communication; Comorbidity; Computer software; Consultations; Country; Data; Data Collection; Diagnosis; Disease; Education; Elderly; End stage renal failure; Enrollment; Ensure; Environment; Epidemiologic Methods; Epidemiologic Studies; Epidemiologist; Epidemiology; Ethnic Origin; Evaluation; Event; Exposure to; Foundations; Funding; General Population; Generations; Geographic Locations; Goals; HIV; HIV Infections; Health Policy; Hepatitis C; Highly Active Antiretroviral Therapy; Hypertension; Immune system; Incidence; Individual; Infection; Instruction; Intention; Investigation; Justice; K-Series Research Career Programs; Kidney Diseases; Life; Malignant Neoplasms; Manuscripts; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Morphologic artifacts; Myocardial Infarction; Observational Study; Oral; Outcome; Participant; Patients; Pharmaceutical Preparations; Population; Population Attributable Risks; Population Study; Positioning Attribute; Preparation; Prevalence; Preventive Intervention; Principal Investigator; Process; Productivity; Protease Inhibitor; Public Health; Public Health Practice; Public Health Schools; Publications; Race; Regimen; Renal carcinoma; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Role; Sample Size; Smoking; Structural Models; Time; Training; United States; Veterans; age related; aged; antiretroviral therapy; base; career; clinical care; clinical practice; cohort; comparison group; effective therapy; high risk; interest; male; medical schools; meetings; multidisciplinary; screening; sex; statistics; symposium

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.

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，研究者的目的是作为一名独立研究者，专注于与年龄相关的合并症（即心肌病）的观察性流行病学研究。 HIV 感染者中的梗塞 [MI]、终末期肾病 [ESRD] 和非艾滋病相关癌症 [癌症]）。迄今为止，该候选人已接受了艾滋病毒和流行病学方法方面的优秀博士培训；她开始将研究兴趣集中在艾滋病毒感染者的合并症上。职业发展奖允许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）在研究问题生成、研究设计、统计分析、结果解释、科学交流和手稿方面的直接指导HIV 流行病学专家 Stephen Gange 博士（导师）进行准备工作，并与 HIV 专家临床医生和研究员 Kelly Gebo 博士（共同导师）一起通过每周会议、半年度目标评估和使用文档共享软件进行生产力跟踪来进行准备； 2) 退伍军人老龄化队列研究 (VACS) 首席研究员 (PI)、艾滋病毒老龄化专家临床医生和流行病学家 Amy Justice 博士、北美艾滋病队列研究与设计合作组织 PI 理查德·摩尔 (Richard Moore) 博士的咨询(NA-ACCORD) 和艾滋病毒临床专家和研究员，以及老年学家和老年人多种疾病研究领导者辛西娅·博伊德 (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、衰老疾病过程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、JHSPH 流行病学系和约翰·霍普金斯医学院 (JHSOM) 的丰富资源环境。近期、短期和长期职业目标包括提高生产力，每年至少发表 5 篇出版物并在科学会议上进行一次口头报告，到 2016 年成功竞争 R01 资助研究老年 HIV 感染者的多重发病率，以及分别作为独立研究人员取得了富有成效的职业生涯。 据估计，2015 年美国艾滋病病毒感染者中有 50% 的年龄将在 50 岁以下。拟议研究的总体目标是通过调查具有临床和公共卫生意义的三个问题来挑战和扩展艾滋病毒老龄化研究的范式：1）与社会人口统计学相似的未感染艾滋病毒的人相比，艾滋病毒感染者是否具有更高的合并症风险个人？ 2) 传统风险因素或 HIV 相关风险因素是否导致 HIV 感染者合并症风险增加？ 3) 开始高效抗逆转录病毒治疗 (HAART) 的时机对合并症风险有什么影响？这些问题将通过调查以下目标来提出： 目标 1：按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的合并症风险差异。目标 2：确定美国和加拿大临床护理中 HIV 感染者合并症的传统风险因素和 HIV 相关风险因素的可归因比例。目标 3：通过美国和加拿大临床护理中 HIV 感染者开始 HAART 时的 CD4 计数来确定开始 HAART 后首次合并症事件的风险。 退伍军人衰老队列研究 (VACS) 是一项针对超过 100,000 名 HIV 感染者和类似未感染患者的纵向、多地点观察性研究，旨在评估 HIV 感染者中与年龄相关的合并症，使其成为研究目标 1 的理想队列尽管这个以男性为主的队列的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的年龄、种族和年龄是匹配的。种族、性别和地理位置，确保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、多地点观察性研究，招募了超过 115,000 名 HIV 感染者，并正在进行 MI、ESRD 和癌症事件的数据收集工作。这种队列合作具有独特的定位，可以解决目标 2 和 3，样本量足够大，可以捕获足够数量的共病事件。 1) VACS 和 NA-ACCORD 数据丰富的环境，2) STATEPI、流行病学部和 JHSOM 资源丰富的环境，以及 3) 由导师和顾问组成的多学科团队可以对这些目标进行调查，挑战并扩展了当前艾滋病毒老龄化的范式，作为候选人作为独立研究调查员取得成功职业生涯的基础。