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Genital-Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women.

Genital-Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women.
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Liebenberg LJ, Masson L, Arnold KB, Mckinnon LR, Werner L, Proctor E, Archary D, Mansoor LE, Lauffenburger DA, Abdool Karim Q, Abdool Karim SS, Passmore JS,


Liebenberg LJ, Masson L, Arnold KB, Mckinnon LR, Werner L, Proctor E, Archary D, Mansoor LE, Lauffenburger DA, Abdool Karim Q, Abdool Karim SS, Passmore JS, (click to view)

Liebenberg LJ, Masson L, Arnold KB, Mckinnon LR, Werner L, Proctor E, Archary D, Mansoor LE, Lauffenburger DA, Abdool Karim Q, Abdool Karim SS, Passmore JS,

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Journal of acquired immune deficiency syndromes (1999) 74(3) 318-325 doi 10.1097/QAI.0000000000001218

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.

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