title: Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.
abstract: BACKGROUND
  Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have anti-inflammatory effects that are independent of their lipid-lowering properties. Despite suppressive antiretroviral therapy (ART), elevated levels of immune activation and inflammation often persist.
  
  
  METHODS
  The Stopping Atherosclerosis and Treating Unhealthy Bone With Rosuvastatin in HIV (SATURN-HIV) trial is a randomized, double-blind, placebo-controlled study, designed to investigate the effects of rosuvastatin (10 mg/daily) on markers of cardiovascular disease risk in ART-treated human immunodeficiency virus (HIV)-infected subjects. A preplanned analysis was to assess changes in markers of immune activation at week 24. Subjects with low-density lipoprotein cholesterol <130 mg/dL and heightened immune activation (%CD8(+)CD38(+)HLA-DR(+) ≥19%, or plasma high-sensitivity C-reactive protein ≥2 mg/L) were randomized to receive rosuvastatin or placebo. We measured plasma (soluble CD14 and CD163) and cellular markers of monocyte activation (proportions of monocyte subsets and tissue factor expression) and T-cell activation (expression of CD38, HLA-DR, and PD1).
  
  
  RESULTS
  After 24 weeks of rosuvastatin, we found significant decreases in plasma levels of soluble CD14 (-13.4% vs 1.2%, P = .002) and in proportions of tissue factor-positive patrolling (CD14(Dim)CD16(+)) monocytes (-38.8% vs -11.9%, P = .04) in rosuvastatin-treated vs placebo-treated subjects. These findings were independent of the lipid-lowering effect and the use of protease inhibitors. Rosuvastatin did not lead to any changes in levels of T-cell activation.
  
  
  CONCLUSIONS
  Rosuvastatin treatment effectively lowered markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.
  
  
  BACKGROUND
  NCT01218802.
authors.affiliation: Case Western Reserve University.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.forename: Norma
authors.initials: N
authors.lastname: Storer
authors.forename: Danielle
authors.initials: D
authors.lastname: Labbato
authors.forename: Brian
authors.initials: B
authors.lastname: Clagett
authors.forename: Janet
authors.initials: J
authors.lastname: Robinson
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D044966:Anti-Retroviral Agents; D005464:Fluorobenzenes; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium
keywords: HIV-1; monocytes; rosuvastatin; tissue factor