The impact of intravenous heroin use on immune activation in treated HIV

静脉注射海洛因对治疗艾滋病毒的免疫激活的影响

基本信息

批准号：
9389070
负责人：
Corrilynn Olesky Hileman
金额：
$ 80.64万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9389070
关键词：
Acquired Immunodeficiency Syndrome Adult Age Bacterial Infections Blood Vessels Buprenorphine CD4 Lymphocyte Count Cardiovascular Diseases Cardiovascular system Cessation of life Chronic Clinical Management Cohort Studies Complex Control Groups Data Enrollment Functional disorder Funding General Population Goals HIV HIV Infections HIV therapy Harm Reduction Health Services Accessibility Hepatitis C Heroin Heroin Users Immune response Immunologic Markers Individual Inflammation Inflammatory Intravenous Knowledge Lead Life Expectancy Link Lymphocyte Malignant Neoplasms Measures Mediating Methadone Myocardial Infarction NF-kappa B Naloxone Natural Immunity Ohio Opioid Participant Pathogenesis Pathway interactions Patients Permeability Persons Pharmaceutical Preparations Phenotype Play Population Provider Recruitment Activity Risk Risk Factors Role Standardization Stroke T-Lymphocyte Time Vascular Diseases Viral Woman adaptive immunity antiretroviral therapy cardiovascular disorder risk cardiovascular risk factor cohort empowered endothelial dysfunction experience heroin overdose high risk high risk behavior/lifestyle immune activation indexing intravenous drug use intravenous drug user medication-assisted treatment men methadone maintenance microbial monocyte mortality opioid use disorder overdose death oxidized lipid prospective sex transmission process treatment program vascular inflammation virology

项目摘要

The proposal in this application will study the extent and specifics of immune activation, its cardiovascular consequences, and mechanisms as they relate to gut integrity in HIV-infected intravenous (IV) heroin users virologically-suppressed on antiretroviral therapy. Overreaching goals are 1) to define the extent and specifics of immune activation in HV-infected IV heroin users; 2) to define the effect of IV heroin on gut integrity and permeability, and the relationship of gut integrity alteration and immune activation; 3) importantly, to study the reversibility of immune activation, inflammation, and gut dysfunction after cessation of IV heroin, and to that effect, compare two strategies for medication assisted treatment—buprenorphine/naloxone versus methadone maintenance; 4) to study if heightened immune activation associated with active intravenous drug use (IVDU) is associated with higher cardiovascular disease risk, including endothelial dysfunction and arterial inflammation, and if these effects are reversible with buprenorphine/naloxone or methadone. To answer these complex questions an expert team has been assembled with the plan to recruit a cohort of ART-treated, HIV- infected persons who use IV heroin, and very carefully matched HIV-infected controls who have never used IV drugs. A second cohort of ART-treated HIV-infected persons who use IV heroin choosing medication assisted treatment with either buprenorphine/naloxone or methadone to stop using will also be established. These cohorts will be followed serially and data will be collected regarding virologic and immunologic responses to continued IV heroin use versus no IVDU and to buprenorphine/naloxone versus methadone. Levels of cellular activation with phenotyping of T-lymphocytes, as well as levels of soluble markers of immune activation and inflammation will be measured. The effect and reversibility of IVDU on arterial inflammation and endothelial dysfunction will be serially measured, before and after buprenorphine/naloxone or methadone.

本应用中的建议将研究免疫激活的程度和细节，其心血管与HIV感染的静脉内（IV）海洛因用户相关的后果和机制病毒学对抗逆转录病毒疗法的抑制作用。超越目标是1）定义范围和规格 HV感染的IV海洛因使用者的免疫激活； 2）定义IV海洛因对肠道完整性的影响渗透性以及肠道完整性改变与免疫激活的关系； 3）重要的是，研究免疫激活，感染和肠道功能障碍的可逆性在停止IV海洛因后，对此效果，比较两种用于药物辅助治疗的策略 - 鲍多宁/纳洛酮与Metagadone 维护; 4）研究是否与主动静脉药使用（IVDU）相关的免疫反应增强（IVDU）与较高的心血管疾病风险有关，包括内皮功能障碍和动脉炎症，如果这些作用是用丁丙诺啡/纳洛酮或方法酮可逆的。回答这些一支专家团队的复杂问题已与计划招募一系列经过艺术治疗的HIV-的计划。使用IV海洛因的感染者，并且非常仔细地匹配从未使用过IV的HIV感染的对照毒品。第二个使用IV海洛因选择药物的艺术治疗的艾滋病毒感染者还将建立用丁丙诺啡/纳洛酮或方法adone停止使用的处理。这些将遵循串行遵循的队列，并将收集有关病毒学和免疫学反应的数据继续使用IV海洛因与IVDU，以及丁丙诺啡/纳洛酮与Metagadone。细胞水平通过T淋巴细胞的表型来激活，以及免疫激活的实心标记水平将测量炎症。 IVDU对人工制品注射和内皮的影响和可逆性功能障碍将在丁丙诺啡/纳洛酮或美沙酮之前和之后串行测量。