CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

796 MATERNAL AND CORD PLASMA BIOACTIVE EICOSANOID PROFILES DIFFER IN HIV+ AND HIV– WOMEN Kayode Balogun 1 , Lauren Balmert 2 , Jennifer Jao 2 , Shan Sun 2 , Richard Bazinet 3 , Lena Serghides 1 1 University Health Network, Toronto, ON, Canada, 2 Northwestern University, Chicago, IL, USA, 3 University of Toronto, Toronto, ON, Canada Background: Pregnant women with HIV (WHIV) are more likely to experience adverse birth outcomes, through mechanisms not fully understood. Eicosanoids play important roles in pregnancy and fetal growth and development, but data are lacking in the context of pregnancy, HIV, and antiretroviral therapy (ART). We examined bioactive eicosanoids (cell-signaling molecules derived from polyunsaturated fatty acids) in maternal and cord plasma from a Canadian cohort of WHIV and HIV negative (HIV-) pregnant women. Methods: 76 maternal samples at gestational week 33-38 (39 WHIV, 37 HIV-) and 55 cord samples (31 WHIV, 24 HIV-) were included. All WHIV received protease inhibitor (PI)-based ART. Levels of 139 eicosanoids were measured using liquid chromatography-mass spec and quantified against standard curves with a lower limit of 0.025ng. Differences between groups for each eicosanoid were assessed using Mann-Whitney test corrected for multiple comparisons using a false discovery rate of 0.05. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to differentiate groups by maternal HIV status. Correlations between eicosanoids in maternal and cord plasma were examined by Spearman r. Results: A total of 53 eicosanoids were detected in maternal and 58 in cord plasma. Cord and maternal eicosanoid profiles differed, with only 3 correlating between compartments among HIV- women and none among WHIV. Compared to the HIV- group, maternal plasma in WHIV had higher levels of circulating arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), and elevated levels of lipoxygenase pathway metabolites including several hydroxyeicosatetraenoic acids (HETEs), which have been associated with inflammatory and vasoconstrictive properties. In cord plasma, only 3 eicosanoids differed significantly between groups. All were vasodilating and pro-angiogenic dihydroxyeicosatrienoic acids (DHETs) (CYP/epoxygenase/ soluble epoxide hydrolase metabolites of AA), and were lower in WHIV. OPLS-DA analysis indicated group separation by eicosanoids with maternal (see figure) and cord specimens. Conclusion: Bioactive eicosanoid profiles differ in maternal and cord plasma, and are altered in pregnant WHIV. Elevated maternal levels of inflammatory lipoxygenase metabolites and lower cord levels of DHETs in the context of HIV/ PI exposure may indicate or contribute to poor placenta function. Our findings also suggest an altered in utero environment that could contribute to fetal programming.

to conception vs. during pregnancy/prior to sample collection vs. no ART prior to sampling) using t-tests and Kruskal-Wallis rank test. We also evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or SGA <10th percentile weight-for-GA) using univariate and multivariate log-binomial regression controlling for age and timing of ART start. Results: Specimens were available for 414 women (372 WLHIV and 42 HIV- negative), with median age 28 years and median gestational age at sample collection 30 weeks (Q1,Q3: 26,35). WLHIV had statistically significantly higher median VCAM1 (p=0.002) than HIV-negative women. HIV-negative women higher median ICAM1 (p=0.01); there was no statistically significant difference in e-Selectin levels. ICAM1 and e-Selectin were not statistically different by ART status or timing. Women starting ART during pregnancy had higher log 10 VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p=0.02) or after (p=0.03) ART initiation. Ninety-eight women (91 WLHIV and 7 HIV-negative) had stillbirth (total 9 mothers) or baby with SGA (total 89 babies). Univariate and adjusted analyses did not show significant associations between levels of any of these biomarkers and adverse birth outcomes (stillbirth or SGA). Conclusion: Maternal HIV infection, and lack of ART or recently starting ART, were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. Markers of endothelial activation were not associated with SGA or stillbirth

Poster Abstracts

797 BREASTMILK MICROBIOME/VIROME OF HIV+ KENYAN WOMEN IS NOT ALTERED BY IMMUNOSUPPRESSION Rabia Maqsood 1 , Jennifer Slyker 2 , LaRinda A.Holland 1 , Lily I.Wu 1 , Ruth Nduati 3 , Dorothy Mbori-Ngacha 4 , Grace John-Stewart 2 , Dara Lehman 5 , Efrem Lim 1 1 Arizona State University, Tempe, AZ, USA, 2 University of Washington, Seattle, WA, USA, 3 University of Nairobi, Nairobi, Kenya, 4 UNICEF, New York, NY, USA, 5 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Background: Breast milk (BM) harbors a diverse community of bacteria (microbiome) and viruses (virome) that are transmitted frommother-to-infant during breastfeeding and are important for establishing a healthy infant gut flora. Whether the BMmicrobiome and virome of women living with HIV are

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