Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy

Clin Infect Dis. 2014 Feb;58(4):588-95. doi: 10.1093/cid/cit748. Epub 2013 Nov 18.

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.

Clinical trials registration: NCT01218802.

Keywords: HIV-1; monocytes; rosuvastatin; tissue factor.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Female
  • Fluorobenzenes / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Placebos / administration & dosage
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Anti-Retroviral Agents
  • Fluorobenzenes
  • Placebos
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium

Associated data

  • ClinicalTrials.gov/NCT01218802