Increased soluble vascular cell adhesion molecule-1 plasma levels and soluble intercellular adhesion molecule-1 during antiretroviral therapy interruption and retention of elevated soluble vascular cellular adhesion molecule-1 levels following resumption of antiretroviral therapy.
OBJECTIVE
We investigated the effect of short viremic episodes on soluble markers associated with endothelial stress and cardiovascular disease risk in chronically HIV-1-infected patients followed during continuous antiretroviral therapy, antiretroviral therapy interruption and antiretroviral therapy resumption.


METHODS
We assessed changes in plasma levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by enzyme-linked immunosorbent assay, as well as T-cell activation (CD8+/CD38+, CD8+/HLA-DR+ and CD3+/CD95+) by flow cytometry, in 36 chronically HIV-1-infected patients participating in a randomized study. Patients were divided into the following three groups: a, on continuous antiretroviral therapy; b, on a 6-week antiretroviral therapy interruption; or c, on antiretroviral therapy interruption extended to the achievement of viral set point.


RESULTS
Although all measurements remained stable over a 40-week follow-up on antiretroviral therapy, plasma levels of soluble vascular cell adhesion molecule-1 (P < 0.0001) and soluble intercellular adhesion molecule-1 (P = 0.003) increased during treatment interruption in correlation with viral rebound and T-cell activation. No significant changes in von Willebrand factor were observed in any of the groups. After resuming antiretroviral therapy, soluble vascular cell adhesion molecule-1 levels remained elevated even after achievement of viral suppression to less than 50 copies/ml.


CONCLUSIONS
The prompt rise in plasma soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 upon viral rebound suggests an acute increase in endothelial stress upon treatment interruption, which may persists after viral resuppression of virus. Thus, viral replication during short-term treatment interruption may increase the overall cardiovascular risk during and beyond treatment interruption.
The Wistar Institute, Philadelphia, PA 19104, USA.
Emmanouil
E
Papasavvas
Livio
L
Azzoni
Maxwell
M
Pistilli
Aidan
A
Hancock
Griffin
G
Reynolds
Cecile
C
Gallo
Joe
J
Ondercin
Jay R
JR
Kostman
Karam
K
Mounzer
Jane
J
Shull
Luis J
LJ
Montaner
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D019562:Viral Load; D014841:von Willebrand Factor / Q000378:metabolism
D019380:Anti-HIV Agents; D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1