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Abstract
Chronic activation of the immune system is a hallmark of progressive HIV infection
and better predicts disease outcome than plasma viral load, yet its etiology remains
obscure. Here, we show that circulating microbial products, likely derived from the
gastrointestinal tract, are a primary cause of HIV-related systemic immune activation.
Circulating lipopolysaccharide, an indicator of microbial translocation, is significantly
increased in chronically HIV-infected individuals and SIV-infected rhesus macaques.
We show that monocytes are chronically stimulated in vivo by increased lipopolysaccharide,
which also correlates with measures of innate and adaptive immune activation. Effective
antiretroviral therapy appears to reduce microbial translocation. Furthermore, in
non-pathogenic SIV infection of sooty mangabeys, microbial translocation does not
seem to occur. These data establish a mechanism for chronic immune activation in the
context of a compromised gastrointestinal mucosal surface and provide novel directions
for therapeutic interventions that modify the consequences of acute HIV infection.