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

这项申请中的提案将研究免疫激活的程度和特异性，其心血管 静脉注射(IV)海洛因吸毒者中与肠道完整性有关的后果和机制 病毒学-抗逆转录病毒治疗被抑制。超越的目标是1)确定范围和细节 2)明确静脉注射海洛因对肠道完整性的影响； 通透性，以及肠道完整性改变与免疫激活的关系；3)重要的是，研究 静脉注射海洛因停药后免疫激活、炎症和肠道功能障碍的可逆性 丁丙诺啡/纳洛酮与美沙酮两种药物辅助治疗方案的疗效比较 维持；4)研究主动静脉注射药物(IVDU)是否导致免疫活性增强 与较高的心血管疾病风险相关，包括内皮功能障碍和动脉 炎症，以及丁丙诺啡/纳洛酮或美沙酮是否可逆转这些影响。要回答这些问题 一个专家团队已经组建了一个复杂的问题小组，计划招募一群接受抗逆转录病毒治疗的艾滋病毒- 使用静脉注射海洛因的感染者，以及非常仔细地匹配从未使用静脉注射的艾滋病毒感染对照 毒品。第二批接受抗逆转录病毒药物治疗的艾滋病毒感染者使用静脉注射海洛因选择辅助药物 丁丙诺啡/纳洛酮或停止使用美沙酮的治疗也将被确立。这些 将连续跟踪队列，并收集有关病毒学和免疫学反应的数据。 继续静脉注射海洛因与不使用静脉注射药物，丁丙诺啡/纳洛酮与美沙酮。蜂窝级别 T淋巴细胞表型的激活以及免疫激活和可溶性标志物的水平 将对炎症进行测量。静脉注射DU对动脉炎症和内皮细胞的影响及其可逆性 功能障碍将在丁丙诺啡/纳洛酮或美沙酮治疗前后进行连续测量。

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.