Persistently elevated levels of von Willebrand factor antigen in HIV infection. Downregulation during highly active antiretroviral therapy.
Levels of circulating von Willebrand factor (vWf) antigen are thought to reflect endothelial involvement in various disorders. In the present study we found markedly elevated plasma levels of vWf in HIV-infected patients demonstrated on both cross-sectional and longitudinal testing. Notably, we found that a persistent rise in vWf antigen was associated with progression of HIV-related disease. This elevation of vWf antigen represented functionally normal vWf as evaluated by plasma FVIII, ristocetin cofactor assay and vWf multimer analyses. While HIV-infected patients showed enhanced platelet activation, platelets did not contribute substantially to the increased vWf levels. The high vWf levels were significantly correlated with high viral load, and during HAART, the pronounced decline in HIV RNA levels was accompanied by a corresponding decrease in vWf. The persistent elevation of functionally normal vWf during HIV infection, most probably reflecting a persistent endothelial cell activation, may have an important role in the pathogenesis of HIV infection.
Aukrust
P
P
Section of Clinical Immunology and Infectious Diseases, and Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway. pal.aukrust@Rikshospitalet.no
Bjørnsen
S
S
Lunden
B
B
Otterdal
K
K
Ng
E C
EC
Ameln
W
W
Ueland
T
T
Müller
F
F
Solum
N O
NO
Brosstad
F
F
Frøland
S S
SS
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000209:etiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D021122:Protein Subunits; D018179:Receptors, Thrombin; D019562:Viral Load; D014841:von Willebrand Factor / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology
D015415:Biomarkers; D010446:Peptide Fragments; D021122:Protein Subunits; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D014841:von Willebrand Factor; D005169:Factor VIII