Effects of HIV, Cocaine, and Prolonged ART Use on Subclinical Cardiovascular Disease

HIV、可卡因和长期使用 ART 对亚临床心血管疾病的影响

基本信息

批准号：
10738836
负责人：
SHENGHAN LAI
金额：
$ 137.43万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10738836
关键词：
Acceleration Address Age Aging Anti-Retroviral Agents Area Atherosclerosis Baltimore Basic Science Behavioral Research Biological Markers Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Chronic Clinical Clinical Research Cocaine Cocaine Users Cohort Studies Collaborations Coronary Arteriosclerosis Coronary Stenosis Creativeness Development Diameter Drug abuse Drug usage Elderly Exposure to Fostering Funding Future Goals Grant HIV HIV Infections HIV/AIDS Heart Diseases Homocysteine Impaired cognition Individual Infection Investigation Investigator-Initiated Research Length Long-Term Effects Longitudinal Studies Maryland Medical National Institute of Drug Abuse Outcome Participant Persons Pharmaceutical Preparations Population Prevention Research Research Personnel Research Priority Resources Risk Factors Substance Use Disorder Substance abuse problem Telomere Shortening Testing Troponin T United States National Institutes of Health antiretroviral therapy cocaine use cognitive function cohort comorbidity coronary computed tomography angiography coronary plaque middle age mortality multidisciplinary platform-independent success telomere young adult

项目摘要

As the age of people living with HIV has been rising steadily due to the success of antiretroviral therapy (ART), and continued new infections, the number of people with HIV in the US is now 1.2 million and continues to rise. Since most older adults living with HIV were infected as young adults or in middle age, long-term effects of HIV and ART are now emerging. HIV/ART-associated comorbidities represent a major challenge for HIV-infected individuals. Of noninfectious comorbidities, coronary artery disease (CAD) has become one of leading causes of death among older people with HIV infection. In addition to CAD traditional risk factors, HIV and ART, cocaine use has been shown to be associated with CAD. In 1999, we received the first NIH grant in the US to investigate the effects of HIV and cocaine use on subclinical atherosclerosis, specifically HIV- associated cardiovascular comorbidity. Since then, 4 NIDA-funded studies by this team were conducted and a cohort of study participants, with/without HIV infection, with/without ART and with/without cocaine use, has been established and followed in Baltimore, Maryland for 17 consecutive years. Pursuing the goal of examining the individual and combined effects of HIV infection, long-term exposure to ART, chronic cocaine use, and other factors on subclinical CAD, we found that cocaine use may induce/accelerate subclinical CAD and other HIV-associated comorbidities. We recently identified several high priority research questions/hypotheses that deserve to be explored thorough collaborations with other investigators: (1) coronary plaque volume may be more sensitive to quantify factors associated with coronary plaque burden, (2) telomere length may be associated with HIV, cocaine use and aging, (3) Troponin T may be a maker for the degree of coronary plaque burden, and (4) homocysteine may be a potentially useful biomarker for HIV/cocaine associated comorbidities. The central objective for this U01 is to further examine whether and how cocaine use influences the HIV/ART- associated CAD and other comorbidities. The specific aims of this proposed study are: (1) to maintain and expand our existing cohort involving HIV/ART and cocaine-associated cardiovascular and other comorbidities as a platform for high priority research and as a platform for other scientific collaborations; (2) to examine longitudinally the effects of HIV, chronic cocaine use, and prolonged ART exposure on the presence, development and progression of CCTA-defined subclinical/clinical CAD, (3) to investigate whether cocaine use exacerbates the HIV-associated decline in cognitive function in HIV-infected cocaine users, (4) to investigate whether HIV and cocaine are associated with telomere shortening, and (5) to examine interrelationships between homocysteine (Hcy) and HIV/ART/cocaine-associated comorbidities. All the hypotheses proposed in this application have not been tested and are crucial to the scientific field of HIV/AIDS and substance abuse. The proposed study will make unique contributions to a better understanding of whether and how drug abuse exacerbates cardiovascular and other comorbidities in those with HIV and substance use disorder.

由于抗逆转录病毒疗法的成功，随着艾滋病毒感染者的年龄一直在稳步上升（艺术），并且持续的新感染，美国艾滋病毒的人数现在为120万上升。由于大多数患有艾滋病毒的老年人被感染为年轻人或中年，所以长期艾滋病毒和艺术的影响现在正在出现。艾滋病毒/与艺术相关的合并症是对艾滋病毒感染者。在非感染性合并症中，冠状动脉疾病（CAD）已成为艾滋病毒感染的老年人死亡的主要原因。除了CAD传统危险因素外，艾滋病毒和艺术，可卡因的使用已被证明与CAD相关。 1999年，我们获得了第一笔NIH赠款美国研究HIV和可卡因对亚临床动脉粥样硬化的影响，特别是HIV- 相关的心血管合并症。从那以后，进行了4项NIDA资助的研究，并研究参与者，患有/没有艾滋病毒感染的研究参与者，有/没有艺术，没有可卡因的使用，连续17年在马里兰州巴尔的摩建立并紧随其后。追求检查的目标艾滋病毒感染，长期暴露于艺术，慢性可卡因的使用以及关于亚临床CAD的其他因素，我们发现可卡因的使用可能诱导/加速亚临床CAD和其他艾滋病毒相关的合并症。我们最近确定了一些高优先研究问题/假设值得与其他研究人员进行彻底合作探索：（1）冠状斑块可能是对与冠状斑块负担相关的量化因素更敏感，（2）端粒长度可能是与HIV，可卡因的使用和衰老相关，（3）肌钙蛋白T可能是冠状动脉斑块的制造商负担和（4）同型半胱氨酸可能是HIV/可卡因相关合并症的潜在有用的生物标志物。该U01的核心目的是进一步研究可卡因的使用以及如何影响HIV/ART- 相关的CAD和其他合并症。这项拟议研究的具体目的是：（1）维护和扩展我们现有的涉及HIV/ART和可卡因相关的心血管和其他合并症的队列作为高优先研究的平台，并作为其他科学合作的平台；（2）检查纵向艾滋病毒，慢性可卡因使用和长时间的艺术暴露对存在的影响， CCTA定义的亚临床/临床CAD的开发和进展，（3）研究可卡因是否使用加剧了感染可卡因使用者的认知功能的HIV相关性下降，（4）调查艾滋病毒和可卡因是否与端粒缩短相关，（5）检查相互关系在同型半胱氨酸（HCY）和HIV/ART/可卡因相关的合并症之间。所有提出的假设该应用尚未进行测试，对于艾滋病毒/艾滋病和滥用毒品的科学领域至关重要。拟议的研究将为更好地理解是否以及如何滥用药物做出独特的贡献在患有艾滋病毒和药物使用障碍的患者中，心血管和其他合并症加剧了心血管和其他合并症。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Circulating levels of cardiac troponin T are associated with coronary noncalcified plaque burden in HIV-infected adults: a pilot study.

DOI：
10.1177/0956462418800873
发表时间：
2019-03
期刊：
International journal of STD & AIDS
影响因子：
1.4
作者：
Foster P;Sokoll L;Li J;Gerstenblith G;Fishman EK;Kickler T;Chen S;Tai H;Lai H;Lai S
通讯作者：
Lai S

Impact of Cardiovascular Disease on Health Insurance Coverage and Healthcare Use under Economic Stress: The National Health and Nutrition Examination Survey, 2003-2012.

经济压力下心血管疾病对健康保险覆盖范围和医疗保健使用的影响：全国健康和营养检查调查，2003-2012 年。