Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D

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 (= 37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNF alpha, IFNy gamma, IL6, IL8, IL1 beta, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Ra, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GRO alpha, MMP9, IL10, TGF beta, 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 sIL2Ra was associated with increased risk of SPTD. High sCD14, GCSF, PGF2 alpha, 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 PGF2 alpha, and lower anti-inflammatory 5-HEPE. Conclusions: The best plasma predictor of SPTD in WLHIV was sIL2R alpha, 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