Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates

Ivona Pandrea, Elaine Cornell, Cara Wilson, Ruy M. Ribeiro, Dongzhu Ma, Jan Kristoff, Cuiling Xu, George S. Haret-Richter, Anita Trichel, Cristian Apetrei, Alan Landay and Russell Tracy
This article has an Erratum 124(6):981


HIV infection is associated with increased risk of cardiovascular complications, the underlying mechanism of which remains unclear. Plasma levels of the coagulation biomarker D-dimer (DD) have been correlated with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of coagulation markers DD and thrombin anti-thrombin (TAT) in pathogenic SIV infections of rhesus (RMs) and pigtailed macaques (PTMs), and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys (SMs). Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In SIVagm-infected PTMs, DD levels were highly indicative of AIDS progression and increased mortality and were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as an ideal animal model for the study of the mechanisms of HIV-associated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection and was strongly correlated with markers of immune activation/inflammation and microbial translocation (MT) and only peripherally associated with VLs. Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced MT and immune activation) resulted in significant increases of DD. Altogether, our data demonstrate that, in SIV infection, hypercoagulation and cardiovascular pathology are at least in part a consequence of excessive immune activation and MT.

  • Submitted March 1, 2012.
  • Accepted May 22, 2012.