title: Genital-Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women.
abstract: BACKGROUND
  Mucosal and systemic immune mediators have been independently associated with HIV acquisition risk, but the relationship between compartments remains unclear.
  
  
  METHODS
  To address this, the concentrations of 12 cytokines were compared in matched plasma and cervicovaginal lavages (CVLs) from 57 HIV-positive women before their acquisition of HIV (cases) and 50 women who remained uninfected (controls) during the CAPRISA 004 trial.
  
  
  RESULTS
  Although genital IP-10 concentrations were significantly higher in cases, plasma IP-10 concentrations were inversely associated with HIV risk. Comparing differences in mucosal and systemic cytokine concentrations between cases and controls, mucosa-biased gradients indicating higher cervicovaginal lavage relative to plasma concentrations were observed for all 5 chemokines in the panel. Four were significantly associated with HIV acquisition, including IP-10 (odds ratio [OR] 1.73, 95% confidence interval [CI]: 1.27 to 2.36), macrophage inflammatory protein-1β (OR 1.72, 95% CI: 1.23 to 2.40), interleukin (IL)-8 (OR 1.50, 95% CI: 1.09 to 2.05), and monocyte chemotactic protein-1 (OR 1.36, 95% CI: 1.01 to 1.83). None of the other 7 cytokines tested predicted HIV risk. Decision tree analyses confirmed this association, with gradients of IP-10, IL-8, and granulocyte-macrophage colony-stimulating factor concentrations correctly classifying 77% of HIV outcomes.
  
  
  CONCLUSIONS
  Our findings suggest that mucosa-biased gradients of IP-10, macrophage inflammatory protein-1β, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.
authors.affiliation: *Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; †Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa; ‡Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa; §Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; ‖Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI; ¶Department of Epidemiology, Columbia University, New York City, NY; and #National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Lenine J P
authors.initials: LJ
authors.lastname: Liebenberg
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Arnold
authors.forename: Lyle R
authors.initials: LR
authors.lastname: Mckinnon
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Proctor
authors.forename: Derseree
authors.initials: D
authors.lastname: Archary
authors.forename: Leila E
authors.initials: LE
authors.lastname: Mansoor
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.forename: Quarraisha
authors.initials: Q
authors.lastname: Abdool Karim
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool Karim
authors.forename: Jo-Ann S
authors.initials: JS
authors.lastname: Passmore
mesh_terms: D000328:Adult; D018925:Chemokines / Q000032:analysis*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D018928:Immunity, Mucosal; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D018925:Chemokines