Statins drugs are powerful anti-inflammatory agents in addition to their known lipid- lowering effects. In the general population, most cardiovascular events occur in subjects with normal or mildly elevated lipid levels, a population previously not targeted for statin therapy. Recently, the landmark JUPITER study changed the face of primary CVD prevention and recently, the FDA expanded the approval of statin therapy to include primary prevention of older subjects with hsCRP >2 mg/L, LDL-cholesterol <130 mg/dL, and one additional cardiovascular risk factor. However, the findings of JUPITER should not be automatically extrapolated to the pro-inflammatory state of HIV. Our hypothesis is that in HIV-infected patients with good virologic control, high CRP and normal LDL-C, rosuvastatin will improve endothelial function and decrease atherogenesis, and that rosuvastatin acts primarily as an anti-inflammatory and anti-oxidant agent. Also, because of the strong link between inflammation and osteoporosis in the general population, and the multiple animal and human studies showing a beneficial effect of statins on bone metabolism, we will use this unique opportunity to examine the effects of statins on skeletal health.
The specific aims will be investigated in a randomized, double-blind, placebo-controlled trial of 140 HIV-infected subjects who are on stable antiretroviral therapy and with good HIV virologic control, with LDL-C <130 mg/dL and hsCRP >2 mg/L. This study is novel in this population, and will have significant implications in future management of people living with HIV, specifically in better refining the indication of statin therapy in primary cardiovascular prevention.

Public Health Relevance

People living with HIV are getting older and suffering from several complications of HIV and its therapy, including increased risk of heart disease and osteoporosis. This study will examine the effect of a potent statin medication on these complications and will aim to understand the driver of these complications in people living with HIV. Our goal is that by using a safe agent, like statins, we will be able to decrease the risk of cardiovascular disease and thin bones in people living with HIV. In addition, we will be able to better understand the role played by chronic inflammation and oxidant stress on these complications.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
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Special Emphasis Panel (ZNR1-REV-M (05))
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Hardy, Lynda R
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Case Western Reserve University
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Eckard, Allison Ross; Jiang, Ying; Debanne, Sara M et al. (2014) Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects receiving antiretroviral therapy. J Infect Dis 209:1156-64
Funderburg, Nicholas T; Jiang, Ying; Debanne, Sara M et al. (2014) Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy. Clin Infect Dis 58:588-95
Longenecker, Chris T; Jiang, Ying; Orringer, Carl E et al. (2014) Soluble CD14 is independently associated with coronary calcification and extent of subclinical vascular disease in treated HIV infection. AIDS 28:969-77
Longenecker, Chris T; Hileman, Corrilynn O; Funderburg, Nicholas T et al. (2014) Rosuvastatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial. Clin Infect Dis 59:1148-56
Erlandson, Kristine M; O?Riordan, Maryann; Labbato, Danielle et al. (2014) Relationships between inflammation, immune activation, and bone health among HIV-infected adults on stable antiretroviral therapy. J Acquir Immune Defic Syndr 65:290-8
Longenecker, Chris T; Dunn, Whitney; Jiang, Ying et al. (2013) Adipokines and vascular health in treated HIV infection: an obesity paradox? AIDS 27:1353-6
Longenecker, C T; Funderburg, N T; Jiang, Y et al. (2013) Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med 14:385-90
Longenecker, Chris T; Jiang, Ying; Yun, Chun-Ho et al. (2013) Perivascular fat, inflammation, and cardiovascular risk in HIV-infected patients on antiretroviral therapy. Int J Cardiol 168:4039-45