The article by Jason M. Brenchley, presented at the 2006 International Meeting of The Institute of Human Virology, discusses the role of microbial translocation in chronic immune activation in HIV infection. The study found that circulating microbial products, likely originating from the gastrointestinal tract, are a primary cause of HIV-related systemic immune activation. Specifically, lipopolysaccharide levels, an indicator of microbial translocation, are significantly elevated in chronically HIV-infected individuals and SIV-infected rhesus macaques. Monocytes are chronically stimulated by increased lipopolysaccharide, correlating with measures of innate and adaptive immune activation. Effective antiretroviral therapy appears to reduce microbial translocation, and in non-pathogenic SIV infection of sooty mangabeys, microbial translocation does not occur. These findings provide a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and suggest new therapeutic directions to modify the consequences of acute HIV infection.The article by Jason M. Brenchley, presented at the 2006 International Meeting of The Institute of Human Virology, discusses the role of microbial translocation in chronic immune activation in HIV infection. The study found that circulating microbial products, likely originating from the gastrointestinal tract, are a primary cause of HIV-related systemic immune activation. Specifically, lipopolysaccharide levels, an indicator of microbial translocation, are significantly elevated in chronically HIV-infected individuals and SIV-infected rhesus macaques. Monocytes are chronically stimulated by increased lipopolysaccharide, correlating with measures of innate and adaptive immune activation. Effective antiretroviral therapy appears to reduce microbial translocation, and in non-pathogenic SIV infection of sooty mangabeys, microbial translocation does not occur. These findings provide a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and suggest new therapeutic directions to modify the consequences of acute HIV infection.