CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

pregnancy intention and barriers to pregnancy planning, will be critical for developing treatment guidelines within DTG-based ART programs.

1 Imperial College London, London, UK, 2 Lewisham and Greenwich NHS Trust, London, UK, 3 Homerton University Hospital NHS Trust, London, UK, 4 North Middlesex University Hospital, London, UK, 5 Chelsea and Westminster Hospital, London, UK, 6 Royal Free Hospital, London, UK, 7 Guy’s and St Thomas’ NHS Foundation Trust, London, UK Background: Term and preterm labour are inflammatory events. Early data indicate that PBMCs migrate to the genital tract to influence inflammation. The genital mucosa-systemic cytokine gradient has been proposed as a surrogate for the migration of PBMCs to the genital mucosa. No data in HIV infected pregnancy are available. We characterized the gradient of cervicovaginal (CVF) cytokines to plasma cytokines in HIV infected and uninfected pregnant women. Methods: CVF, plasma and PBMCs were isolated from HIV uninfected (n=27) and cART treated, infected (n=48) pregnant women in the 2nd trimester. Concentrations of 10 cytokines in CVF and plasma were measured using multiplex immunoassays. Flow cytometry was performed for T cell surface markers: CD4, CD8, HLA-DR and CD25. Maternal characteristics, immunovirologic parameters and pregnancy outcome were recorded. Gradients were compared by HIV status, cART exposure, prematurity and correlations with T cell subsets and gestational age at delivery were explored. Results: All measured genital-plasma cytokine gradients were greater in HIV infected than uninfected pregnant women p<0.0001, largely driven by high CVF cytokine concentrations (Table). In HIV infected women: the greatest gradients observed were for pro-inflammatory cytokine IL-1β and chemokine IL-8, followed by IL-2; CD4 cell % correlated positively with inflammatory IL-2 gradient (rho=0.28, p=0.01) and immune-regulatory IL-13 (rho=0.23, p=0.04); CD25+ T cell subsets associated inversely with IL-1β gradient (CD4+CD25+%; rho=-0.30, p=0.003; CD8+CD25+%; rho=-0.26, p=0.03); CD4:CD8 ratios correlated positively with IL-2 gradient (rho=0.25, p=0.02) and CD4+HLA- DR+% correlated inversely with IL-2 gradient (rho=-0.28, p<0.01). In this small sample no association between genital-plasma cytokine gradient with cART exposure or gestational age at delivery was observed. Conclusion: HIV infected women have elevated genital mucosal cytokine gradients compared to uninfected women during the 2nd trimester pregnancy notably IL-1b and IL-8; both known for their role in preterm labour initiation. Activated CD25+T cell subsets were inversely correlated with IL-1b suggesting a regulatory role in genital inflammation. The role of genital inflammation and its regulation warrants further investigation in adverse pregnancy outcomes in HIV infected women.

793 METABOLITES, PRETERM LABOR, AND ANTIRETROVIRAL THERAPY Nicole H. Tobin 1 , Aisling Murphy 1 , Fan Li 1 , Sean S. Brummel 2 , Mary Glenn Fowler 3 , James A.McIntyre 4 , Judith S. Currier 1 , Tsungai Chipato 5 , Patricia M. Flynn 6 , Brian Koos 1 , Grace M. Aldrovandi 1 , for the 1077BF/1077FF PROMISE (Promoting Maternal and Infant Survival Everywhere) Team 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Anova Health Institute, Johannesburg, South Africa, 5 University of Zimbabwe, Harare, Zimbabwe, 6 St. Jude Children's Research Hospital, Memphis, TN, USA Background: Antiretroviral treatment (ART) has significantly reduced AIDS-related deaths, however, ART, including protease inhibitors, has been associated with an increased risk of preterm birth (PTB). In PROMISE, PTB (<37 weeks) occurred in 20.5% of pregnancies where mothers received zidovudine, lamivudine, lopinavir-ritonavir (PI) versus 13.1%where mothers received zidovudine alone (ZDV), p<0.001. To date the mechanisms involved in ART- associated PTB remain elusive. Methods: Untargeted metabolomics was performed on maternal plasma and dried blood spots (DBS), and infant DBS from 100 mother-infant pairs enrolled in PROMISE; 50 preterm and 50 term deliveries, divided evenly between ZDV or PI. Maternal samples were obtained at the timepoint closest but prior to preterm delivery with controls matched for gestational age (GA) at sampling. Infant DBS were earliest available. Linear regression and random forests (RF) models were used to identify metabolic predictors of PTB. Results: The mean GA at delivery was 33.1 weeks (Preterm) and 40.0 weeks (Term) and at sample collection 30.4, 30.5, 31.0 and 31.0 weeks for Preterm ZDV, Term ZDV, Preterm PI, and Term PI, respectively. DBS from one collection site separated from all others and were dropped because they were deemed unreliable (N=21 pairs, 9 preterm and 12 term). RF models for PTB using maternal plasma metabolite levels achieved out-of-bag accuracies of 86.1% and 79.1% for the ZDV and PI groups, respectively. Similar results were achieved with maternal DBS profiles (83.3% and 83.7% accuracy). Key predictors of PTB in the ZDV group identified by both RF and linear regression analyses included increased levels of 17a-hydroxypregnanolone glucuronide, methionine sulfone, pantothenate, and urate. PTB in the PI group was associated with increased nucleotide and amino acid metabolism (7-methylguanine, N2,N2- dimethylguanosine, N-acetylputrescine, methionine sulfone). RF models using infant metabolite profiles from the first 3 days of life (N=61) achieved 79.2% and 83.8% accuracy for PTB classification showing decreases in infant steroid metabolism in both the ZDV and PI groups. Conclusion: In this exploratory study of HIV infected gravidas receiving ART, untargeted metabolomics identified perturbations in both steroid hormone metabolism and nucleotide/ amino acid metabolism that predict PTB. Untargeted metabolomics may be an effective strategy for identifying potential mechanisms of PTB associated with ART, and warrants further investigation. 794 GENITAL TRACT & PLASMA CYTOKINES & SYSTEMIC T-CELL ACTIVATION IN HIV+ PREGNANT WOMEN Charlotte-Eve S. Short 1 , Rachael A. Quinlan 1 , Robin J. Shattock 1 , Judith Russell 2 , Brenton Wait 3 , Christopher Wood 4 , David Hawkins 5 , Rimi Shah 6 , Pippa Farrugia 7 , Phillip R. Bennett 1 , Graham P. Taylor 1 , for the London HIV Pregnancy Research Group

Poster Abstracts

795 MATERNAL BIOMARKERS OF ENDOTHELIAL DYSFUNCTION BY HIV/ART STATUS AND BIRTH OUTCOMES Gaerolwe Masheto 1 , Sikhulile Moyo 1 , Terence Mohammed 1 , Christina Banda 1 , Charlene Raphaka 1 , Mompati O.Mmalane 1 , Joseph Makhema 1 , Roger L. Shapiro 2 , Mosepele Mosepele 3 , Rebecca Zash 4 , Shahin Lockman 5 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 University of Botswana, Gaborone, Botswana, 4 Beth Israel Deaconess Medical Center, Boston, MA, USA, 5 Brigham and Women's Hospital, Boston, MA, USA Background: Women living with HIV (WLHIV) are at higher risk of having an adverse birth outcomes, with underlying mechanism(s) unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth. Methods: We used previously-collected data and samples fromWLHIV and HIV-negative women enrolled during pregnancy in the observational Botswana Tshipidi cohort. We measured plasma levels of markers endothelial activation [soluble vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-selectin] from samples taken during pregnancy. We compared log biomarker levels by maternal HIV status and by timing of ART initiation (prior

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