title: Genital inflammation and the risk of HIV acquisition in women.
abstract: BACKGROUND
  Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group.
  
  
  METHODS
  Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial.
  
  
  RESULTS
  HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3-7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines.
  
  
  CONCLUSIONS
  Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town.
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town National Health Laboratory Services, Cape Town, South Africa.
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Lenine J
authors.initials: LJ
authors.lastname: Liebenberg
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Baxter
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Arnold
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Department of Statistical Sciences, University of Cape Town.
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Leila E
authors.initials: LE
authors.lastname: Mansoor
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Vivek
authors.initials: V
authors.lastname: Naranbhai
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: National Research Foundation of South Africa/Department of Science and Technology Centre of Excellence for TB Biomedical Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, South Africa.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ronacher
authors.affiliation: National Research Foundation of South Africa/Department of Science and Technology Centre of Excellence for TB Biomedical Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, South Africa.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Garrett
authors.affiliation: Center for Infection and Immunity.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Williams
authors.affiliation: Center for Infection and Immunity.
authors.forename: Mara
authors.initials: M
authors.lastname: Couto-Rodriguez
authors.affiliation: Center for Infection and Immunity.
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.affiliation: Center for Infection and Immunity.
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban.
authors.forename: Anneke
authors.initials: A
authors.lastname: Grobler
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Quarraisha
authors.initials: Q
authors.lastname: Abdool Karim
authors.affiliation: Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool Karim
mesh_terms: D000349:Africa; D002584:Cervix Uteri / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood / Q000276:immunology; D018925:Chemokines / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D005831:Genital Diseases, Female / Q000175:diagnosis*; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood / Q000276:immunology; D012749:Sexually Transmitted Diseases; D013019:South Africa; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood / Q000276:immunology; D002575:Uterine Cervicitis / Q000175:diagnosis; D014621:Vagina / Q000276:immunology; D044364:Vaginal Douching; D014627:Vaginitis / Q000175:diagnosis; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; C508609:IL10 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: HIV transmission; cytokine; female genital tract; inflammation