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Brief Report

Markers of Spontaneous Preterm Delivery in Women Living With HIV

Relationship With Protease Inhibitors and Vitamin D

Weinberg, Adriana MDa; Huo, Yanling MSb; Kacanek, Deborah ScDb; Patel, Kunjal DSc, MPHb; Watts, D. Heather MDc; Wara, Diane MDd; Hoffman, Risa M. MD, PhDe; Klawitter, Jelena PhDf; Christians, Uwe MD, PhDf for IMPAACT P1025 Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1, 2019 - Volume 82 - Issue 2 - p 181–187
doi: 10.1097/QAI.0000000000002111
Clinical Science

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.

aDepartments of Pediatrics, Medicine and Pathology, Anschutz Medical Center, University of Colorado Denver, Aurora, CO;

bDepartment of Biostatistics, Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, Boston, MA;

cNational Institute of Child Health and Human Development, Bethesda, MD;

dUniversity of California San Francisco, San Francisco, CA;

eDivision of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA; and

fDepartment of Anesthesiology, iC42 Clinical Research and Development, University of Colorado Anschutz Medical Campus, Aurora, CO.

Correspondence to: Adriana Weinberg, MD, Departments of Pediatrics, Medicine and Pathology, Anschutz Medical Center, University of Colorado Denver, Mail Stop 8604, 12700 E, 19th Avenue, Room 11126, Aurora, CO 80045 (e-mail:

Supported by NIH grant. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). Support for the laboratory assays was provided by NICHD (Westat contract number 63009715). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The authors have no conflicts of interest to disclose.

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Received February 14, 2019

Accepted May 18, 2019

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