Predictive Biomarkers of CVD Risk in Diverse HIV-1+ Cocaine Abusers

不同 HIV-1 可卡因滥用者 CVD 风险的预测生物标志物

• 批准号: 8921160
• 负责人: Deborah Lynne Jones
• 金额: $ 62.19万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921160
• 关键词: African American; Antibodies; Biological Markers; CD34 gene; Calibration; Cardiac; Cardiovascular Diseases; Carotid Arteries; Caucasians; Chronic Disease; Classification; Cocaine; Cocaine Abuse; Comorbidity; Complication; Corticotropin; Data; Early Diagnosis; Endocrine; Equation; Female; Florida; Foundations; HIV; HIV-1; Health; Hispanics; Hydrocortisone; Immunologics; Individual; Infection; Inflammation; Inflammatory; Insulin; Insulin Resistance; Interleukin-1; Interleukin-6; Intervention; Investigation; Lead; Measurement; Measures; Methods; Participant; Pathway interactions; Plasma; Population; Predictive Value; Protease Inhibitor; Recruitment Activity; Relative (related person); Reporting; Risk; Risk Factors; Sampling; Sexual Transmission; Stem cells; Surrogate Markers; TNF gene; Testing; Thyroid Gland; Treatment outcome; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factors; Woman; aged; base; cardiovascular disorder risk; circulating DNA; conventional therapy; drug abuser; high risk; high risk sexual behavior; immune activation; inflammatory marker; intimal medial thickening; male; men; response; seropositive; standard of care; therapy design

DESCRIPTION (provided by applicant): Florida ranks third in HIV cases in the US, in part due to the association of cocaine abuse with risky sexual behavior and transmission of HIV-1. Although HIV-1 infection treated with cART is now a chronic disease, HIV- related co-morbidities such as cardiovascular disease (CVD) have emerged as a new challenge, particularly among HIV infected - cocaine abusers. Conventional methods to determine CVD risk, e.g., Framingham Risk Scores, may not be as effective in identifying risk in this younger, HIV- infected group as these methods do not take into consideration abnormalities in the inflammatory pathways, cardiac endothelial functions, endocrines and immune activation that occur in HIV and cocaine abuse. This application hypothesizes that HIV-1 infection and cocaine abuse lead to a higher risk of developing CVD due to disturbances in these biomarkers and that the conventional ADA /NCEP based standard of care (SOC) may be less effective in reducing CVD risk in this population. To test this hypothesis, this 5-year application proposes to conduct a cross-sectional investigation of a total of 600 men and women, African Americans, Caucasians, and Hispanics, in 4 groups: HIV-1+ -cocaine abusers (n=200); HIV-1- -cocaine abusers (n=100); HIV-1+ - non- cocaine abusers (n=100); and, HIV-1- - non-cocaine abusers, control, (n=200). All participants will undergo measurement of carotid artery intima-media thickness (IMT), and those identified at high risk of CVD will be referred for SOC treatment and re-assessed after 24 months. AIM 1: To conduct carotid IMT measurement among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). AIM2: To evaluate insulin resistance, inflammatory and immunologic biomarkers, and endothelial progenitor cells as predictors of CVD risk, as defined by IMT: a: To investigate insulin resistance among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). b: To investigate inflammatory markers (plasma CRP, IL-1, IL-6, and TNF-α) among HIV-1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers (control). c: To investigate the surrogate markers of immune activation, sCD14, sCD163 and LPS, among HIV- 1+ cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers. d: To investigate circulating endothelial progenitor cells, EPCs, (CD34+ -VEGFR+), circulating immature-endothelial progenitor cells (CD133+ - VEGFR+), and levels of plasma VEGFR in all study groups. AIM 3: To compare the response to ADA/NCEP SOC intervention at 24 months by study group (HIV-1+ - cocaine abusers, HIV-1- cocaine abusers, HIV-1+ non-cocaine abusers, HIV-1- non-cocaine abusers) evaluating biomarkers (insulin, immune activation, progenitor cells) and IMT.

描述（由申请人提供）：佛罗里达州的 HIV 病例数在美国排名第三，部分原因是可卡因滥用与危险性行为和 HIV-1 传播有关，尽管使用 cART 治疗的 HIV-1 感染现在是一种慢性疾病。心血管疾病 (CVD) 等与 HIV 相关的并发症已成为一项新的挑战，特别是在 HIV 感染者中，确定 CVD 风险的传统方法（例如弗雷明汉风险评分）可能并不那么有效。确定这一年轻的艾滋病毒感染人群的风险，因为这些方法没有考虑艾滋病毒和可卡因滥用中发生的炎症途径、心脏内皮功能、内分泌和免疫激活的异常，从而导致患心血管疾病的风险更高。这些生物标志物的干扰，以及基于 ADA /NCEP 的传统护理标准 (SOC) 在降低该人群的 CVD 风险方面可能效果较差。为了检验这一假设，这项为期 5 年的应用。提议对总共 600 名男性和女性、非洲裔美国人、白人和西班牙裔进行横断面调查，分为 4 组： HIV-1+ 可卡因滥用者（n=200）； n=100）；HIV-1+ - 非可卡因滥用者（n=100）；以及 HIV-1- - 非可卡因滥用者，对照（n=200）。将接受颈动脉内膜中层厚度 (IMT) 测量，那些被确定为 CVD 高风险的患者将被转介接受 SOC 治疗并在 24 个月后重新评估 目标 1：对 HIV-1+ 可卡因进行颈动脉 IMT 测量。滥用者、HIV-1- 可卡因滥用者、HIV-1+ 非可卡因滥用者、HIV-1- 非可卡因滥用者（对照） AIM2：评估胰岛素抵抗、炎症和炎症。根据 IMT 的定义，免疫生物标志物和内皮祖细胞作为 CVD 风险的预测因子：a：调查 HIV-1+ 可卡因滥用者、HIV-1- 可卡因滥用者、HIV-1+ 非可卡因滥用者、HIV-1 1- 非可卡因滥用者（对照）b：调查 HIV-1+ 可卡因滥用者、HIV-1- 中的炎症标志物（血浆 CRP、IL-1、IL-6 和 TNF-α）。可卡因滥用者、HIV-1+ 非可卡因滥用者、HIV-1- 非可卡因滥用者（对照） c：研究 HIV-1+ 可卡因滥用者、HIV 中免疫激活的替代标记物、sCD14、sCD163 和 LPS。 -1- 可卡因滥用者、HIV-1+ 非可卡因滥用者、HIV-1- 非可卡因滥用者 d：研究循环内皮祖细胞，所有研究组中的 EPC、(CD34+ -VEGFR+)、循环未成熟内皮祖细胞 (CD133+ - VEGFR+) 和血浆 VEGFR 水平 目标 3：比较研究组在 24 个月时对 ADA/NCEP SOC 干预的反应。 HIV-1+ - 可卡因滥用者、HIV-1- 可卡因滥用者、HIV-1+ 非可卡因滥用者、HIV-1-非可卡因滥用者）评估生物标志物（胰岛素、免疫激活、祖细胞）和 IMT。