Lopinavir-Ritonavir: Effects on Endothelial Cell Function in Healthy Subjects

• Published in: The Journal of infectious diseases Vol. 193; no. 11; pp. 1516 - 1519
• Main Authors: Grubb, Jessica R., Dejam, André, Voell, Jocelyn, Blackwelder, William C., Sklar, Peter A., Kovacs, Joseph A., Cannon, Richard O., Masur, Henry, Gladwin, Mark T.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.06.2006; University of Chicago Press; Oxford University Press
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Adult; Antiretrovirals; Atherosclerosis; Biological and medical sciences; Blood; Blood flow; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Female; Forearm; Forearm - blood supply; Fundamental and applied biological sciences. Psychology; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV/AIDS; Humans; Infectious diseases; Lopinavir; Male; Medical sciences; Microbiology; omega-N-Methylarginine - administration & dosage; omega-N-Methylarginine - pharmacology; Percentage change; Protease inhibitors; Pyrimidinones - administration & dosage; Pyrimidinones - adverse effects; Regional Blood Flow; Ritonavir - administration & dosage; Ritonavir - adverse effects; Sodium; Infection; Antiretroviral agent; Endothelial cell; Microbiology; Ritonavir; Lopinavir; Antiviral
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/503807

To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non–human immunodeficiency virus–infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment’s effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P=.03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by NG-monomethyl-l-arginine. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction