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.
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.
|Eckard, Allison Ross; Meissner, Eric G; Singh, Inderjit et al. (2016) Cardiovascular Disease, Statins, and HIV. J Infect Dis 214 Suppl 2:S83-92|
|Park, Michelle S; Hileman, Corrilynn O; Sattar, Abdus et al. (2016) Incidental findings on chest computed tomography are common and linked to inflammation in HIV-infected adults. Antivir Ther :|
|Hileman, Corrilynn O; Turner, Randi; Funderburg, Nicholas T et al. (2016) Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV. AIDS 30:65-73|
|Longenecker, Chris T; Eckard, Allison R; McComsey, Grace A (2016) Statins to improve cardiovascular outcomes in treated HIV infection. Curr Opin Infect Dis 29:1-9|
|Morrison, Justin T; Longenecker, Chris T; Mittelsteadt, Alison et al. (2016) Effect of rosuvastatin on plasma coenzyme Q10 in HIV-infected individuals on antiretroviral therapy. HIV Clin Trials 17:140-6|
|Erlandson, Kristine M; Jiang, Ying; Debanne, Sara M et al. (2016) Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy. AIDS Res Hum Retroviruses 32:311-6|
|Hileman, Corrilynn O; Overton, Edgar T; McComsey, Grace A (2016) Vitamin D and bone loss in HIV. Curr Opin HIV AIDS 11:277-84|
|Funderburg, Nicholas T; Boucher, Morgan; Sattar, Abdus et al. (2016) Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy. Pathog Immun 1:118-128|
|Longenecker, Chris T; Sattar, Abdus; Gilkeson, Robert et al. (2016) Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection. AIDS 30:2195-203|
|Lipshultz, Hannah M; Hileman, Corrilynn O; Ahuja, Sanjay et al. (2015) Anaemia is associated with monocyte activation in HIV-infected adults on antiretroviral therapy. Antivir Ther 20:521-7|
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