CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: We measured preprandial insulin levels at 6 weeks of life from dried blood spots (DBS) via direct sandwich ELISA technique and calculated Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) scores in Cameroonian HEU and HUU infants from 2011- 2014. Demographic, clinical, and in utero and postnatal ARV exposure data were collected. Acylcarnitines (ACs) and branch-chain amino acids (BCAAs) were measured via tandemmass spectrometry. We used principal component analysis (PCA) to consolidate the ACs and BCAAs into 5 uncorrelated clusters. We used linear regression models to assess the association of in utero HIV/ARV exposure and infant insulin while adjusting for confounders and PCA-derived AC/BCAA component scores. Results: Of 366 infants, 156 were HEU. Mothers of HEU infants were older (30 vs. 28 years, p <0.01), more often single (23 vs. 12%, p =0.02), and more likely to have had only primary/secondary education levels ( p =0.04). Maternal body mass index (BMI), blood pressure, and gestational diabetes rates did not differ between groups. Birth weight z scores, prematurity rates, and weight-for-age z (WAZ) scores also did not differ, but length-for-age z and head circumference-for-age z scores were lower in HEU infants at 6 weeks (0.42 vs. 0.91, p =0.05 & 0.30 vs. 0.75, p =0.01 respectively). Median insulin levels and HOMA-IR scores were lower in HEU infants (3.6 vs. 4.9 μ IU/mL, p <0.01 & 0.87 vs. 1.12, p <0.01 respectively). Two PCA components differed significantly between groups: Component 3 comprised of AC C2, C3, C4, C5, C6, C4OH, C5OH, C3DC, C4DC, C5DC, and C10 ( p =<0.01) and Component 5 comprised of BCAA (leucine, isoleucine, valine, p =0.04). In multivariate modeling HEU status remained associated with lower infant insulin [ β =(-0.06), p =0.04). Furthermore, infant WAZ ( β =0.04, p <0.01), Component 3 ( β =0.06, p <0.01) & Component 5 ( β =0.03, p =0.02) were associated with higher insulin levels.

Conclusions: Compared to HUU, HEU infants have lower insulin levels at 6 weeks of life. Distinguishing clusters of short-chain ACs and BCAAs were also associated with infant insulin levels. Future studies should determine the significance of these early metabolic changes on later health and morbidity. 881 No Effect of Maternal HIV and In-Utero cART on Infant Leukocyte Telomere Length Abhinav Ajaykumar 1 ; Hugo Soudeyns 2 ; Fatima Kakkar 2 ; Jason Brophy 3 ; Ari Bitnun 4 ; Ariane Alimenti 1 ; Deborah Money 1 ; Arianne Albert 5 ; Hélène C. Côté 1 On behalf of the CIHRTeam in Cellular Aging and HIV Comorbidities inWomen and Children (CARMA) 1 University of British Columbia, Vancouver, Canada; 2 Université de Montréal, Montreal, Canada; 3 University of Ottawa, Ottawa, Canada; 4 University of Toronto, Toronto, Canada; 5 Women’s Health Research Institute, Vancouver, Canada Background: Maternal combination antiretroviral therapy (cART) in pregnancy could have long-term effects on HIV-exposed uninfected (HEU) children. Some antiretrovirals and HIV proteins inhibit telomerase, the enzyme that elongates telomeres. We previously reported shorter leukocyte telomere length (LTL) in HIV+ adults compared to HIV- controls but saw no association with duration of cART. Among children (0-19y) and infants (0-3d) however, no difference in LTL was seen between HIV+, HEU and HIV-unexposed uninfected (HUU) controls, although among HIV+ children, being on cART was associated with longer LTL, and HEU cord blood trended toward shorter LTL. As LTL is a marker of cellular aging and has been linked to age-related morbidities, our objective was to compare HEU and HUU infant LTL at birth and over the first six years of life in this larger cohort and investigate any relationship to cART exposure. Methods: Of 324 HEU children aged 0-3y enrolled in the CARMA cohort study, most (n=215) had ≥ 2 blood samples collected. HUU controls (0-3y, n=308) had a single blood sample each. LTL was measured on whole blood DNA via monochrome multiplex qPCR. A subset of 0-3y HEU and HUU children were randomly age- and sex-matched 1:1. Factors associated with LTL were investigated using linear regression modeling. Results: A cross-sectional analysis of LTL at birth (0-3d) in 115 HEU (56%male) and 91 HUU (54%male) infants considered HIV exposure status, infant sex, gestational age, maternal age, race/ethnicity and smoking ever in pregnancy as explanatory variables. Male sex was associated with shorter LTL at birth (p=0.02), and there was a significant interaction between HEU/HUU status and maternal smoking (p=0.009) with the latter being associated with longer LTL in HUU and shorter LTL in HEU. Among HEU, neither duration of cART exposure in utero nor type of cART was related to birth LTL. There was no difference in LTL attrition rate during the first six weeks of life. Furthermore, among age and sex-matched children (n=214:214), LTL attrition rate was not significantly different between groups (p=0.69), but there was a significant sex by age effect with males having slower attrition than females (p=0.03). Conclusions: These results further support that exposure to maternal HIV/cART in utero does not affect infant LTL, a reassuring finding. It is unclear how exposure to maternal smoking affects LTL; the opposite associations seen here may represent a sampling artifact or a surrogate for other factors. 882 Long-Term Effects of In Utero ARV Exposure on Cardiac Function in HIV-Exposed Uninfected Youth Vitor C. Guerra 1 ; Erin Leister 2 ; Paige L.Williams 2 ; Steven E. Lipshultz 3 ; RussellVan Dyke 1 ; Rohan Hazra 4 ; Steven D. Colan 5 1 Tulane University, New Orleans, LA, US; 2 Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, US; 3 Wayne State University School of Medicine, Detroit, MI, US; 4 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, US; 5 Boston Children’s Hospital, Harvard Medical School, Boston, MA, US Background: Most evaluations of cardiac function in children born to mothers with HIV have focused on infants and children. However, as combination antiretroviral (ARV) regimens become more widely used during pregnancy, potential long-term cardiac effects of in utero ARV exposures warrant monitoring. We evaluated the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children.

Poster Abstracts

531

CROI 2015