Rosuvastatin Treatment Reduces Markers of Monocyte Activation in HIV-Infected Subjects on Antiretroviral Therapy

• Published in: Clinical infectious diseases Vol. 58; no. 4; pp. 588 - 595
• Main Authors: Funderburg, Nicholas T., Jiang, Ying, Debanne, Sara M., Storer, Norma, Labbato, Danielle, Clagett, Brian, Robinson, Janet, Lederman, Michael M., McComsey, Grace A.
• Format: Journal Article
• Language: English
• Published: Oxford OXFORD UNIVERSITY PRESS 15.02.2014; Oxford University Press
• Subjects: Adult; AIDS; Anti-Inflammatory Agents - therapeutic use; Anti-Retroviral Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Antiretrovirals; Antiviral agents; Biological and medical sciences; Biomarkers; Clinical trials; Diabetes; Disease risks; Drug therapy; Female; Fluorobenzenes - therapeutic use; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - immunology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Monocytes; Monocytes - immunology; Pharmacology. Drug treatments; Placebos; Placebos - administration & dosage; Pyrimidines - therapeutic use; RNA; Rosuvastatin Calcium; Statins; Sulfonamides - therapeutic use; T lymphocytes; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Immunopathology; Antiretroviral agent; Monocyte; Enzyme; Enzyme inhibitor; AIDS; Statin derivative; Rosuvastatin; Hypocholesterolemic agent; Immune deficiency; Infection; Chemotherapy; Treatment; HMG-CoA reductase inhibitor; Viral disease; Hydroxymethylglutaryl-CoA reductase; Antiviral; Oxidoreductases; Antilipemic agent; HIV-1; monocytes; tissue factor; rosuvastatin
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cit748

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.