Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy

HIV Med. 2009 Nov;10(10):627-33. doi: 10.1111/j.1468-1293.2009.00733.x.

Abstract

Objectives: To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)-containing regimen in HIV-1-infected individuals already receiving combination antiretroviral therapy (ART).

Methods: Thirty-five HIV-1-infected individuals who switched ART to an ABC-containing regimen were identified. Twenty-two HIV-1-infected individuals who switched ART from and to a non-ABC-containing regimen served as controls. Plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP9), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) were measured in blood samples before the switch in ART, and 3 months and 12 months afterwards. Log10-transformed data were compared with paired t-tests.

Results: Median MMP9 increased from 45.5 to 64.4 microg/mL after 3 months of ABC exposure (P = 0.011) and remained increased after 12 months (64.2 microg/mL; P = 0.013). MPO increased from median 8.8 to 10.4 microg/mL (P = 0.036) after 3 months of ABC exposure but was not increased after 12 months of exposure (9.1 microg/mL). hs-CRP increased from 3.3 to 4.2 microg/mL after 3 months (P = 0.031) but was not increased after 12 months of exposure (2.8 microg/mL). Neither sVCAM-1 nor sICAM-1 changed after the initiation of ABC. No changes were observed in the control group.

Conclusions: MMP9, MPO and hs-CRP all increased after a switch in ART to an ABC-containing regimen. This indicates increased cardiovascular risk in viral load-suppressed HIV-1-infected individuals switching to ABC and proposes a proinflammatory potential as the underlying pathogenetic mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Retroviral Agents / adverse effects
  • Anti-Retroviral Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / chemically induced
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Longitudinal Studies
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Peroxidase / blood
  • Risk Factors
  • Vascular Cell Adhesion Molecule-1 / blood
  • Viral Load
  • Zidovudine / adverse effects

Substances

  • Anti-Retroviral Agents
  • Biomarkers
  • Dideoxynucleosides
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Zidovudine
  • C-Reactive Protein
  • Peroxidase
  • Matrix Metalloproteinase 9
  • abacavir