Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

BMC Infect Dis. 2011 Feb 4:11:40. doi: 10.1186/1471-2334-11-40.

Abstract

Background: Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir.

Methods: Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status.

Results: 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant.

Conclusion: Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / immunology
  • Coagulants / blood
  • Coagulants / immunology
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • Humans
  • Inflammation Mediators / blood
  • Inflammation Mediators / immunology*
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / immunology
  • Tenofovir
  • Thrombosis / etiology
  • Thrombosis / immunology*
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Cell Adhesion Molecule-1 / immunology

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Coagulants
  • Dideoxynucleosides
  • Inflammation Mediators
  • Interleukin-6
  • Organophosphonates
  • Plasminogen Activator Inhibitor 1
  • Vascular Cell Adhesion Molecule-1
  • C-Reactive Protein
  • Tenofovir
  • Adenine
  • abacavir