Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection

L Masson, KB Arnold, F Little, K Mlisana… - Sexually transmitted …, 2016 - sti.bmj.com
L Masson, KB Arnold, F Little, K Mlisana, DA Lewis, N Mkhize, H Gamieldien, S Ngcapu…
Sexually transmitted infections, 2016sti.bmj.com
Background Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV)
cause genital inflammation and increase the risk of HIV infection. WHO-recommended
syndromic STI and BV management is severely limited as many women with asymptomatic
infections go untreated. The purpose of this cross-sectional study was to evaluate genital
cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic,
treatable infections. Methods Concentrations of 42 cytokines in cervicovaginal lavages from …
Background
Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increase the risk of HIV infection. WHO-recommended syndromic STI and BV management is severely limited as many women with asymptomatic infections go untreated. The purpose of this cross-sectional study was to evaluate genital cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic, treatable infections.
Methods
Concentrations of 42 cytokines in cervicovaginal lavages from 227 HIV-uninfected women were measured using Luminex. All women were screened for BV by microscopy and STIs using molecular assays. Multivariate analyses were used to identify cytokine profiles associated with STIs/BV.
Results
A multivariate profile of seven cytokines (interleukin (IL)-1α, IL-1β, tumour necrosis factor-β, IL-4, fractalkine, macrophage-derived chemokine, and interferon-γ) most accurately predicted the presence of a treatable genital condition, with 77% classification accuracy and 75% cross-validation accuracy (sensitivity 72%; specificity 81%, positive predictive value (PPV) 86%, negative predictive value (NPV) 64%). Concomitant increased IL-1β and decreased IP-10 concentrations predicted the presence of a treatable genital condition without a substantial reduction in predictive value (sensitivity 77%, specificity 72%, PPV 82% and NPV 65%), correctly classifying 75% of the women. This approach performed substantially better than clinical signs (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%).
Conclusions
Supplementing syndromic management with an assessment of IL-1β and IP-10 as biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection.
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