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

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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.