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

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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 (PAl-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 PAl-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-based antiretroviral therapy, perhaps as a consequence of improvement in HIV-related inflammation. This improvement occurred independent of development of insulin resistance, which occurred only with indivinavir.

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Authors and Affiliations

  1. Department of Medicine and Division of Infectious Diseases, Indiana University School of Medicine, 1001 W. 10th Street, Suite OPW-430, 46202-2879, Indianapolis, IN

    Erika M. Young & Michael P. Dubé MD

  2. Department of Medicine and Division of Endocrinology, Indiana University School of Medicine, Indianapolis, IN

    Robert V. Considine, Mark A. Deeg, Mikako Degawa-Yamauchi & Sudha Shankar

  3. Department of Medicine and Division of Infectious Disease, University of Southern California, Los Angeles, CA

    Fred R. Sattler & Hannah Edmondson-Melançon

  4. Department of Medicine and Division of Endocrinology, University of Southern California, Los Angeles, CA

    Thomas A. Buchanan

  5. Glaxo Smith Kline, Research Triangle Park, NC

    Jaime Hernandez

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  1. Erika M. Young
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Correspondence to Michael P. Dubé MD.

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Young, E.M., Considine, R.V., Sattler, F.R. et al. Changes in thrombolytic and inflammatory markers after initiation of indinavir- or amprenavir-based antiretroviral therapy. Cardiovasc Toxicol 4, 179–186 (2004). https://doi.org/10.1385/CT:4:2:179

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  • DOI: https://doi.org/10.1385/CT:4:2:179

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