Journal Article

No Impairment of Endothelial Function or Insulin Sensitivity with 4 Weeks of the HIV Protease Inhibitors Atazanavir or Lopinavir-Ritonavir in Healthy Subjects without HIV Infection: A Placebo-Controlled Trial

Michael P. Dubá, Changyu Shen, Martha Greenwald and Kieren J. Mather

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 47, issue 4, pages 567-574
Published in print August 2008 | ISSN: 1058-4838
Published online August 2008 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/590154
No Impairment of Endothelial Function or Insulin Sensitivity with 4 Weeks of the HIV Protease Inhibitors Atazanavir or Lopinavir-Ritonavir in Healthy Subjects without HIV Infection: A Placebo-Controlled Trial

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

Background. Dyslipidemia alone does not fully explain the increase in cardiovascular events among patients receiving protease inhibitor (PI)-based treatment for human immunodeficiency virus infection. Some PIs, such as indinavir, directly induce endothelial dysfunction, an effect that may mediate that portion of the increase in cardiovascular events that is not attributable to dyslipidemia.

Methods. Endothelium-dependent vasodilation, insulin-mediated vasodilation, and whole-body and leg glucose uptake during use of a 1-h euglycemic hyperinsulinemic clamp (insulin infusion, 40 mU/m2/min) were measured in healthy men before and after 4 weeks of treatment with placebo (12 men), with 400 mg atazanavir per day (9 men), or with 400 mg lopinavir and 100 mg ritonavir twice per day (9 men).

Results. Median age (36 years) and mean body mass index ± SD (23.4±2.6; calculated as weight in kilograms divided by the square of height in meters) did not differ between groups. Endothelium-dependent vasodilation, expressed as the percentage change in the leg blood flow response to intrafemoral artery infusion of 15 ≪g/min of the endothelium-dependent vasodilator methacholine, did not change after 4 weeks of treatment in any group: mean percentage change ± SD, 154±102 from baseline and 242±254 at week 4 with atazanavir (P=.36), 76±62 and 86±79, respectively, with lopinavir-ritonavir (P=.68), and 111±86 and 127±153, respectively, with placebo (P=.63; for between-group differences, P=.55). The response to the endothelium-independent vasodilator nitroprusside was not different at week 4 for any group, nor was insulin-mediated vasodilation or leg or whole-body insulin-mediated glucose uptake (all within-group P values were >.1).

Conclusions. Unlike the dramatic impairment seen with indinavir, the newer PIs atazanavir and lopinavir-ritonavir do not induce endothelial dysfunction in healthy subjects. Thus, endothelial dysfunction does not appear to be a PI drug class effect. The cause of the non-lipid-mediated increase in cardiovascular events that are reported with PIs remains unclear.

Journal Article.  3788 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.