Genital Inflammation and the Risk of HIV Acquisition in Women

• Published in: Clinical infectious diseases Vol. 61; no. 2; pp. 260 - 269
• Main Authors: Masson, Lindi, Passmore, Jo-Ann S., Liebenberg, Lenine J., Werner, Lise, Baxter, Cheryl, Arnold, Kelly B., Wiliamson, Carolyn, Little, Francesca, Mansoor, Leila E., Naranbhai, Vivek, Lauffenburger, Douglas A., Ronacher, Katharina, Walzi, Gerhard, Garrett, Nigel J., Williams, Brent L., Couto-Rodriguez, Mara, Hornig, Mady, Lipkin, W. Ian, Grobler, Anneke, Karim, Quarraisha Abdool, Karim, Salim S. Abdool
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.07.2015
• Subjects: Africa; Cervix Uteri - immunology; Chemokine CCL2 - analysis; Chemokine CCL2 - blood; Chemokine CCL2 - immunology; Chemokines - analysis; Chemokines - blood; Chemokines - genetics; Chemokines - immunology; Cytokines; Cytokines - analysis; Cytokines - blood; Cytokines - genetics; Cytokines - immunology; Disease Susceptibility; Female; Genital Diseases, Female - diagnosis; Genitalia, Female - immunology; Genitalia, Female - virology; HIV; HIV Infections - immunology; HIV Infections - transmission; HIV Infections - virology; HIV/AIDS; Human immunodeficiency virus; Humans; Inflammation - diagnosis; Inflammatory diseases; Interferon; Interferon-gamma - analysis; Interferon-gamma - blood; Interferon-gamma - immunology; Interleukin-10 - analysis; Interleukin-10 - immunology; Interleukin-6 - analysis; Interleukin-6 - blood; Interleukin-6 - immunology; Interleukin-8 - analysis; Interleukin-8 - blood; Interleukin-8 - immunology; Sexually Transmitted Diseases; South Africa; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - immunology; Urogenital system; Uterine Cervicitis - diagnosis; Vagina - immunology; Vaginal Douching; Vaginitis - diagnosis; Women; Young Adult; South Africa; Africa; cytokine; female genital tract; inflammation; HIV transmission
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/civ298

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.