Changes in thrombolytic and inflammatory markers after initiation of indinavir- or amprenavir-based antiretroviral therapy

Cardiovascular Toxicology
Erika M YoungMichael P Dubé

Abstract

HIV-infected subjects who have lipodystrophy and insulin resistance on prolonged antiretroviral therapy have elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens, markers of impaired thrombolysis that are associated with hyperinsulinemia and increased cardiovascular risk. We studied HIV-infected, protease inhibitor (PI)-naive adults treated with indinavir (n = 11) or amprenavir (n = 14) plus two nucleoside reverse transcriptase inhibitors enrolled in two independent prospective trials. Antiretroviral and immune responses were similar in both studies. Over 8 wk, indinavir was associated with decreased insulin sensitivity, whereas amprenavir was not. Levels of tPA antigen declined by approx 25% with both treatments (p < 0.05 for each); levels of PAI-1 antigen did not change. Levels of the inflammatory marker soluble tumor necrosis factor-alpha receptor II (sTNFr2) correlated positively with tPA antigen (r = 0.33, p = 0.02), and mean (SD) plasma concentrations of sTNFr also declined with treatment (4.44 +/- 1.11 ng/mL pretherapy, 3.75 +/- 1.21 posttherapy, p = 0.007). Short-term improvement in a marker of impaired thrombolysis and increased vascular risk can occur during PI-b...Continue Reading

Citations

Oct 12, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jason V BakerUNKNOWN INSIGHT SMART Study Group
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Steen B Haugaard
Jun 15, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Michael P Dubé, Joseph J Cadden
Jan 10, 2009·International Journal of Cardiology·Jean-Jacques MonsuezDaniel Vittecoq
Sep 19, 2006·Metabolism: Clinical and Experimental·Ellen S EngelsonDonald P Kotler
Oct 28, 2010·Current Opinion in HIV and AIDS·Jason V Baker, Daniel Duprez

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