Adriana Weinberg1, Yanling Huo2, Deborah Kacanek2, Kunjal Patel2, D Heather Watts3, Diane Wara4, Risa M Hoffman5, Jelena Klawitter6, Uwe Christians6. 1. Departments of Pediatrics, Medicine and Pathology, Anschutz Medical Center, University of Colorado Denver, Aurora, CO. 2. Department of Biostatistics, Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, Boston, MA. 3. National Institute of Child Health and Human Development, Bethesda, MD. 4. University of California San Francisco, San Francisco, CA. 5. Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. 6. Department of Anesthesiology, iC42 Clinical Research and Development, University of Colorado Anschutz Medical Campus, Aurora, CO.
Abstract
BACKGROUND: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. DESIGN: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1β, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFβ, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. RESULTS: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. CONCLUSIONS: The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.
BACKGROUND:Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. DESIGN: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1β, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFβ, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. RESULTS:Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin Dinsufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. CONCLUSIONS: The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.
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