HIV Cardiac Risk Reduction and CD24Fc (CALIBER)

这项研究是一项2期随机、安慰剂对照、双盲临床试验，目的是评估CD24Fc在HIV患者中的安全性和耐受性，以及CD24Fc对HIV患者低密度脂蛋白(LDL)变化的影响。我们还将评估CD24Fc对总胆固醇和甘油三酯、免疫激活标志物(T细胞激活、sCD14和炎性细胞因子)、HIV储存库大小、HbA1c和瘦素以及肝脏脂肪变性等炎症标志物的影响。 我们假设CD24Fc对接受抗逆转录病毒治疗的HIV患者是安全和可耐受的，并能显著降低低密度脂蛋白。此外，我们假设CD24Fc将降低接受ART治疗的慢性HIV患者的胆固醇、瘦素、糖化血红蛋白、肝脏脂肪变性和纤维化以及炎症标志物。 在这项第二阶段的研究中，一组艾滋病毒患者将以1：1的方式随机接受CD24Fc与安慰剂的静脉注射，在为期4周的治疗窗口中，每2周注射一次CD24Fc，随后进行24周的随访期。 在24周的随访期内，患者将被跟踪观察安全性和不良事件，以及脂代谢和炎症标志物的变化。这项调查将在马里兰大学和国立卫生研究院进行。 这项由美国国立卫生研究院临床中心完成的研究是马里兰大学研究的一部分，目的是通过PET/CT对动脉FDG的标准化摄取值来评估CD24Fc对主动脉血管炎症的影响。12名低密度脂蛋白-125(低密度脂蛋白，也称为坏胆固醇水平较高)的受试者将被选择接受选择性FDG PET/CT扫描。治疗前后将评估动脉FDG摄取FDG-PET/CT所证实的血管炎症的变化。动脉对FDG的摄取是通过标准化摄取值(SUV)最大值除以静脉SUV平均值得出的靶与背景比(TBR)来衡量的。 扫描完成了两次，一次是在开始研究药物之前，另一次是在完成研究药物24周后。FDG PET/CT扫描将有助于确定服用研究药物或安慰剂后血管中的炎症水平是否有任何变化。 当COVID对患者收益的限制取消时，这项研究将开始登记。

This study is a phase 2, randomized, placebo-control, double-blinded clinical trial to assess the safety and tolerability of CD24Fc among patients with HIV, and the effect of CD24Fc on change in low-density lipoprotein (LDL) among patients with HIV. We will also evaluate the effect of CD24Fc on total cholesterol and triglycerides, markers of immune activation (T cell activation, sCD14, and inflammatory cytokines), size of HIV reservoirs, HbA1c and leptin, and hepatic steatosis, among other inflammatory markers. We hypothesize that therapy with CD24Fc will be safe and tolerable in HIV patients on ART, and result in significant decreases in LDL. In addition, we hypothesize that CD24Fc will reduce cholesterol, leptin, HbA1c, hepatic steatosis and fibrosis, and markers of inflammation in patients with chronic HIV who are virally suppressed on ART. In this phase 2 study, a cohort of 64 HIV patients virally suppressed on ART will be randomized in a 1:1 fashion to receive an intravenous infusion of 240mg of CD24Fc vs. placebo administered every 2 weeks during a 4-week treatment window, followed by a 24- week follow-up period. Patients will be followed for safety and adverse events as well as changes in lipid metabolism and inflammatory markers during a 24-week follow-up period. This investigation will take place at the University of Maryland and National Institutes of Health. The research being completed at the National Institutes of Health Clinical Center as part of the University of Maryland study is to assess the effect of CD24Fc on aortic vascular inflammation as measured by standardized uptake value of arterial FDG by PET/CT. Twelve subjects with an LDL>125 (a high level of low-density lipoproteins (LDL), also known as bad cholesterol) will be selected to have an optional FDG PET/CT scan. Change in vascular inflammation as evidenced by aortic FDG uptake by FDG-PET/CT will be assessed before and after therapy. The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR). This scan is completed twice, once before starting the study drug, and again 24 weeks after completing the study drug. The FDG PET/CT scans will help to determine if there are any changes to the levels of inflammation in the blood vessels after taking the study drug, or placebo. This study will start enrolling when COVID restrictions on patient accrual are removed.