Treatment outcomes and comorbidity in HIV-infected IDU

2 K24 DA 035684-06A1 这是为格雷戈里·卢卡斯博士重新提交的以患者为导向的研究(K24)职业生涯中期奖的竞争性续签申请。卢卡斯博士是约翰·霍普金斯大学的医学教授。他接受过传染病专家的医学培训，并在彭博公共卫生学院获得了临床调查博士学位。20年来，他的研究有两个重点：1)艾滋病毒、丙型肝炎病毒和药物使用与肾脏和心血管疾病的关系，以及2)在美国和其他地方改善注射吸毒者(PWID)艾滋病毒预防和治疗结果的干预措施。在之前的资助期间，卢卡斯博士对指导和领导做出了重大承诺，同时保持了研究和资助生产率的良好记录。这一续签申请的目标是继续支持指导初级调查人员的计划，并通过跨学科团队建设促进创新研究。该研究战略提出了三个积极的研究平台，使受训人员参与与艾滋病毒和PWID相关的研究。这三个家长目标概述了目前得到资助的工作，这些工作将作为K24提案的框架。每个母公司的目标都与一个新提出的扩展目标相关联，该目标为初级研究人员提供了所有权机会。卢卡斯博士是巴尔的摩一项队列研究的PI，该研究目前处于第二个资助期，旨在表征艾滋病毒、丙型肝炎病毒和可卡因使用在肾脏和心血管疾病中的作用(父母目标1)。这个队列是独一无二的，在384名参与者中进行了1200次碘己醇肾小球滤过率(IGFR)测量，并进行了长达6年的随访。相关的扩展目标1建议确定与基于肌酐和胱抑素C估计艾滋病毒阳性者的GFR斜率的准确性相关的因素。家长目标2是一项整群随机试验，评估综合护理车(ICV)在向巴尔的摩的PWID提供与PWID和HIV相关的循证服务方面的有效性。扩展目标2建议评估在ICV上提供丙型肝炎病毒评估和治疗的可行性，并在试点随机试验中比较将社区招募的丙型肝炎病毒感染的PWID转诊到ICV或城市卫生部门诊所(标准护理)的策略。 家长目标3描述了一个正在进行的大型研究组合，重点是改善国际环境中关键人群的艾滋病毒预防和治疗结果。扩展目标3建议评估受访者驱动的抽样，将其作为一种干预工具，以确定不知情/已出院的艾滋病毒阳性预激综合征。约翰霍普金斯大学在艾滋病毒和药物使用相关研究方面的出色环境和资源是这一提议的关键背景。最后，卢卡斯博士建议进行培训，以支持他的职业发展和团队建设，以领导对美国阿片类药物流行的多学科研究。

2 K24 DA 035684-06A1 This is a resubmission of a competing renewal application for a mid-career investigator award in patient- oriented research (K24) for Dr. Gregory Lucas. Dr. Lucas is a Professor of Medicine at Johns Hopkins University. He is medically trained as an infectious diseases specialist and he completed a PhD in clinical investigation at the Bloomberg School of Public Health. For 20 years, his research has had a dual focus: 1) associations of HIV, HCV, and drug use on kidney and cardiovascular disease, and 2) interventions to improve HIV prevention and treatment outcomes among people who inject drugs (PWID) in the US and elsewhere. In the previous funding period, Dr. Lucas made a major commitment to mentoring and leadership, while maintaining a strong track record of research and funding productivity. The objectives of this renewal application are to continue to support a program for mentoring junior investigators and to foster innovative research through interdisciplinary team building. The research strategy presents three active research platforms for engaging trainees in HIV- and PWID-related research. These three Parent Aims outline currently funded work that will serve as the framework for the K24 proposal. Each Parent Aim is linked to a newly proposed Expansion Aim that provides ownership opportunity for a junior researcher. Dr. Lucas is PI of a Baltimore-based cohort study, now in its second funding period, designed to characterize the roles of HIV, HCV, and cocaine use in kidney and cardiovascular disease (Parent Aim 1). This cohort is unique in having over 1200 iohexol glomerular filtration rate (iGFR) measurements in 384 participants, with up to 6 years of follow-up. The linked Expansion Aim 1 proposes to determine factors associated with the accuracy of creatinine- and cystatin C-based estimation of GFR slope in HIV-positive persons. Parent Aim 2 is a cluster- randomized trial evaluating the effectiveness of an integrated care van (ICV) in providing PWID- and HIV- related evidence-based services to PWID in Baltimore. Expansion Aim 2 proposes to assess the feasibility of providing HCV evaluation and treatment on the ICV and to compare strategies of referring community-recruited HCV-infected PWID to the ICV or to a city health department clinic (standard care) in a pilot randomized trial. Parent Aim 3 describes a large and ongoing research portfolio focused on improving HIV prevention and treatment outcomes in key populations in international settings. Expansion Aim 3 proposes to assess respondent-driven sampling as an interventional tool to identify unaware/out-of-care HIV-positive PWID. The outstanding environment and resources for HIV- and drug use-related research at Johns Hopkins are a key backdrop to this proposal. Finally, Dr. Lucas proposes training to support his career development and team building to lead a multidisciplinary research response to the opioid epidemic in the US.