SWITCH TO ATAZANAVIR AND BRACHIAL ARTERY REACTIVITY (SABAR) STUDY: ENDOTHELIA

改用阿扎那韦和肱动脉反应性 (SABAR) 研究：内皮细胞

• 批准号: 7717576
• 负责人: Michael Phillip Dube
• 金额: $ 0.48万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717576
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Anti-Retroviral Agents; Atazanavir; Atherosclerosis; Blood; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Case Study; Central obesity; Cholesterol; Class; Clinical; Complication; Computer Retrieval of Information on Scientific Projects Database; Coronary Arteriosclerosis; Development; Drug usage; Employee Strikes; Endothelium; Event; Fasting; Fatty acid glycerol esters; Flow-It; Functional disorder; Funding; Future; Grant; HIV; HIV-1; Heart Diseases; Hyperglycemia; Hyperlipidemia; Immunologics; Individual; Institution; LDL Cholesterol Lipoproteins; Literature; Mediating; Medical; Metabolic; Morbidity - disease rate; Patients; Plasma; Protease Inhibitor; Purpose; Randomized; Research; Research Personnel; Resources; Risk Factors; Source; Thinking; Treatment Protocols; Triglycerides; United States National Institutes of Health; Vasodilation; Vial device; Virus Diseases; Week; abstracting; antiretroviral therapy; brachial artery; mortality; size; viral RNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human immunodeficiency virus (HIV) protease inhibitors (PIs) confer striking immunologic and clinical benefits that have led to their widespread acceptance as key components of antiretroviral therapy in patients with HIV infection. Unfortunately, up to 60% of patients receiving HIV PIs develop hyperlipidemia, hyperglycemia, and central obesity. Because these morphological and metabolic changes adversely affect several risk factors for atherosclerotic vascular disease, there is concern that cardiovascular disease may become an important acquired immune deficiency syndrome (AIDS)-related complication. Case reports of severe premature coronary artery disease (CAD) in patients receiving HIV PIs already have appeared in the medical literature. Use of HIV PIs has been associated with endothelial dysfunction, an early and initiating step in atherosclerosis that predicts future adverse cardiovascular events. The primary objective of this study is to compare the change in brachial artery flow mediated vasodilation (FMD) from baseline to week 24 in subjects switching to ATV with the change in brachial artery FMD in subjects continuing on a stable antiretroviral regimen. In this study, HIV-infected subjects on a stable protease inhibitor (PI) containing antiretroviral regimen with plasma HIV RNA <500 copies/mL, who have fasting LDL cholesterol levels >130 mg/dL or fasting triglycerides levels >200 mg/dL, will be randomized (1:1) to continue their current antiretroviral regimen or to switch the PI to atazanavir (ATV) for 24 weeks. ABSTRACT IN LAY TERMS Protease inhibitors (PIs), a class of drugs used to treat HIV infection, have resulted in impressive improvements in human immunodeficiency virus-1 (HIV)-related morbidity and mortality. Unfortunately, up to 60% of individuals receiving PIs develop elevated fat levels in their blood (triglycerides or LDL cholesterol), which are associated with the development of heart disease. The use of PIs has also been associated with reduced ability of blood vessels to relax, and therefore the inside of the vessel stays small. This can cause changes in cholesterol-containing substances in the blood when it flows through the smaller-sized vessel and is thought to possibly contribute to the development of heart disease. The purpose of this study is to determine the effects of switching the current protease inhibitor therapy to atazanavir therapy on how well the blood vessels relax (endothelial function). HIV-infected subjects on a stable protease inhibitor (PI) containing antiretroviral regimen with HIV vial load <500 copies/mL, who have fasting LDL cholesterol levels >130 mg/dL or fasting triglycerides levels >200 mg/dL, will be assigned by chance to continue their current antiretroviral regimen or to switch the PI to atazanavir (ATV) for 24 weeks.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人类免疫缺陷病毒（HIV）蛋白酶抑制剂（PI）具有显著的免疫学和临床益处，已被广泛接受为HIV感染患者抗逆转录病毒治疗的关键组成部分。 不幸的是，高达60%的接受HIV PI的患者发展为高脂血症、高血糖症和向心性肥胖。 由于这些形态和代谢变化对动脉粥样硬化血管疾病的几个危险因素产生不利影响，因此人们担心心血管疾病可能成为重要的获得性免疫缺陷综合征（AIDS）相关并发症。 接受HIV PI的患者发生严重早发冠状动脉疾病（CAD）的病例报告已经出现在医学文献中。 使用HIV PI与内皮功能障碍有关，内皮功能障碍是动脉粥样硬化的早期和起始步骤，可预测未来的不良心血管事件。本研究的主要目的是比较转换为ATV的受试者中肱动脉血流介导的血管舒张（FMD）从基线至第24周的变化与继续接受稳定抗逆转录病毒治疗方案的受试者中肱动脉FMD的变化。 在本研究中，接受稳定的含蛋白酶抑制剂（PI）的抗逆转录病毒治疗方案且血浆HIV RNA <500拷贝/mL、空腹LDL胆固醇水平>130 mg/dL或空腹甘油三酯水平>200 mg/dL的HIV感染受试者将随机（1：1）继续接受当前的抗逆转录病毒治疗方案或将PI转换为阿扎那韦（ATV）治疗24周。 用通俗的话讲摘要 蛋白酶抑制剂（PI）是一类用于治疗HIV感染的药物，已导致人类免疫缺陷病毒-1（HIV）相关发病率和死亡率的显著改善。 不幸的是，高达60%的接受PI的个体在他们的血液中产生脂肪水平升高（甘油三酯或LDL胆固醇），这与心脏病的发展有关。PI的使用也与血管松弛能力降低有关，因此血管内部保持较小。当血液流经较小的血管时，这可能会导致血液中含胆固醇物质的变化，并被认为可能有助于心脏病的发展。本研究的目的是确定将目前的蛋白酶抑制剂治疗转换为阿扎那韦治疗对血管舒张（内皮功能）的影响。 接受稳定的含蛋白酶抑制剂（PI）的抗逆转录病毒方案且HIV小瓶载量<500拷贝/mL的HIV感染受试者，空腹LDL胆固醇水平>130 mg/dL或空腹甘油三酯水平>200 mg/dL，将随机分配继续其当前的抗逆转录病毒方案或将PI转换为阿扎那韦（ATV）24周。