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Rosuvastatin Reduces Immune Activation and Inflammation in Treated HIV Infection
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CROI: Rosuvastatin Improves Hip Bone Mineral Density but Worsens Insulin Resistance - (03/07/14)
Reported by Jules Levin
CROI 2014 March 3-6 Boston, MA
Nicholas T. Funderburg1, Brian Clagett2, Ying Jiang2, Sara M.Debanne2, Norma Storer2, Danielle Labbato2, Steven Juchnowski2, Brian Ferrari, Michael Lederman2, Grace A. McComsey21
1The Ohio State University School of Health and Rehabilitation Sciences2Case Western Reserve University,University Hospitals Case Medical Center, Cleveland, OH, USA
Program Abstract-
Background: Despite suppressive antiretroviral therapy (ART), elevated levels of immune activation and inflammation often persist in HIV-infected
subjects. Statins have anti-inflammatory effects, and when given in combination with ART, may reduce immune activation.
Methodology: The 96-week Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN-HIV) trial is a randomized,
double-blind, placebo-controlled trial to evaluate the effect of statins on markers of cardiovascular risk and skeletal health in HIV. This was a pre-planned
analysis of the effect of rosuvastatin at week 48 on immune activation and inflammation. All subjects were on ART, and had HIV-1 RNA<1000 copies/mL,
LDL-cholesterol <30mg/dL and evidence of immune activation (C8+CD38+DR+ >19% or hsCRP >2mg/L). Randomization was 1:1 to daily rosuvastatin
10 mg or placebo, and was stratified by protease inhibitor (PI) use. Tcell activation was measured by expression of CD38, HLA-DR, and PD1. Monocyte
activation was measured with soluble markers (sCD14 and sCD163) and by real time enumeration of monocyte subpopulations and tissue factor (TF)
expression. We also measured markers of systemic inflammation (hsCRP, sTNF-RI and II, IL-6, IP-10, sVCAM-1 and ICAM-1), vascular inflammation (Lp-
PLA2), and coagulation (D-dimer, fibrinogen).
Results: 147 subjectsenrolled; 78% male, 70% black, 29% white, with median age 47 years and CD4 cells 613 cells/μL; 49% were on PI and 78%
had HIV-1 RNA <50 copies/mL. Baseline characteristics were similar between groups, except for the % of CD14DimCD16+ monocytes that expressed
TF (statin= 21.8% and placebo= 18.9%, p=0.05).
Rosuvastatin use reduced sCD14 (p=0.006), Lp-PLA2 (p=0.0007), and IP-10 (p=0.03) levels. In addition, sCD163 and fibrinogen decreased within the
statin arm (p=0.001 and p=0.015). The %TF+ CD14DimCD16+ monocytes was also reduced in the statin arm compared to the placebo arm (p=0.005).
Within the statin arm, treatment reduced proportions of TF+ monocytes among all three subsets (CD14+CD16-, p=0.002, CD14+CD16+ and CD14DimCD16+,
p<0.0001 for both).
There was also a greater decrease in the proportions of activated T cells between the placebo and statin arms (p=0.009 for CD4+ cells
and p=0.003 for CD8+ cells).
Conclusions: 48 weeks of rosuvastatin treatment reduced significantly several markers of inflammation and lymphocyte and
monocyte activation in ARTtreated subjects, whether these favorable changes translate to a clinical benefit remains to be elucidated.
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