Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy.
OBJECTIVE
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.
Kristoffersen
U S
US
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark. ulriksk@mfi.ku.dk
Kofoed
K
K
Kronborg
G
G
Benfield
T
T
Kjaer
A
A
Lebech
A-M
AM
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000139:chemically induced; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects; D000099227:Abacavir
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D015224:Dideoxynucleosides; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9; D009195:Peroxidase; D019010:Vascular Cell Adhesion Molecule-1; D015215:Zidovudine; D000099227:Abacavir