Lindi Masson1, Jo-Ann S Passmore2, Lenine J Liebenberg3, Lise Werner3, Cheryl Baxter3, Kelly B Arnold4, Carolyn Williamson1, Francesca Little5, Leila E Mansoor3, Vivek Naranbhai3, Douglas A Lauffenburger4, Katharina Ronacher6, Gerhard Walzl6, Nigel J Garrett3, Brent L Williams7, Mara Couto-Rodriguez7, Mady Hornig7, W Ian Lipkin7, Anneke Grobler3, Quarraisha Abdool Karim8, Salim S Abdool Karim8. 1. 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. 2. 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. 3. Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban. 4. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. 5. Department of Statistical Sciences, University of Cape Town. 6. 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. 7. Center for Infection and Immunity. 8. 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.
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.
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.
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