title: Microbial translocation is a cause of systemic immune activation in chronic HIV infection.
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, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P <or= 0.002). We show that increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy seemed to reduce microbial translocation partially. Furthermore, in nonpathogenic SIV infection of sooty mangabeys, microbial translocation did not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide new directions for therapeutic interventions that modify the consequences of acute HIV infection.
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.forename: Tedi E
authors.initials: TE
authors.lastname: Asher
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.forename: Zachary
authors.initials: Z
authors.lastname: Kazzaz
authors.forename: Ethan
authors.initials: E
authors.lastname: Bornstein
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Daniel
authors.initials: D
authors.lastname: Altmann
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Leia
authors.initials: L
authors.lastname: Teixeira-Johnson
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018988:Bacterial Translocation / Q000502:physiology*; D016665:Cercocebus atys; D002908:Chronic Disease; D004755:Enterobacteriaceae / Q000502:physiology*; D005243:Feces / Q000382:microbiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity
chemical_list: D019380:Anti-HIV Agents; D008070:Lipopolysaccharides