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 re flect endothelial involvement in various disorders. In the present study we found markedly elevated plasma levels of vWf in HIV-infected patients demo nstrated on both cross-sectional and longitudinal testing. Notably, we foun d 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 ac tivation, platelets did not contribute substantially to the increased vWf l evels. The high vWf levels were significantly correlated with high viral lo ad, and during HAART, the pronounced decline in HIV RNA levels was accompan ied by a corresponding decrease in vWf. The persistent elevation of functio nally normal vWf during HIV infection, most probably reflecting a persisten t endothelial cell activation, may have an important role in the pathogenes is of HIV infection.