CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

829 CARDIOVASCULAR RISK PROFILE: A CLINIC-BASED SAMPLE OF YOUTH LIVING WITH HIV IN THE US Sitaji Gurung 1 , Kit N. Simpson 2 , Christian Grov 3 , H.Jonathon Rendina 1 , Terry T. Huang 3 , Stephen Scott Jones 1 , Marshall Chew 2 , Tyra Dark 4 , Sylvie Naar 4 1 Hunter College, CUNY, New York, NY, USA, 2 Medical University of South Carolina, Charleston, SC, USA, 3 City University of New York, New York, NY, USA, 4 University of Florida College of Medicine, Tallahassee, FL, USA Background: Accelerated atherosclerosis has been found in young individuals diagnosed with HIV. Previous research indicates that lower CD4 and higher plasma viral load (VL) significantly increased the risk of cardiovascular disease (CVD); however, this link is largely under-investigated among youth living with HIV (YLH). We examined whether detectable VL and low CD4 increased the risk of CVD among YLH aged 14-26y. Methods: This study used electronic health records from the Adolescent Medicine Trials Network 154 Cascade Monitoring baseline data extracted frommultidisciplinary adolescent HIV care settings across the United States. Multivariable linear regression was used to assess the association between detectable VL and CD4 of ≤ 200 with Cardiac Risk Score1 (for those who had systolic blood pressure, cigarette smoking, diabetes, and anti-hypertensive medication use data, n =813) and Cardiac Risk Score2 (for those who had systolic blood pressure, cigarette smoking, diabetes, anti-hypertensive medications use, total cholesterol, and HDL data, n = 398) adapted from the Framingham gender-specific algorithm. Results: The sample was predominantly black and male with mean age of 21y. Overall, 47.8% had a detectable VL and 8.6% had a baseline CD4 of ≤ 200 indicating immune dysfunction. In bivariate analyses, both scores (Cardiac Risk Score1, p < 0.001; Cardiac Risk Score2, p < 0.01) demonstrated significantly increased risk of CVD in patients who had detectable VL compared with those who had undetectable VL. Comparing patients who had CD4 ≤ 200 with those who had CD4 > 200, the risk of CVD was significantly increased in patients who had CD4 ≤ 200 compared with those who had CD4 > 200 using Cardiac Risk Score2 (p < 0.01) but not Cardiac Risk Score1. In the multivariable models, after adjusting for demographic and clinical covariates, a log 10 increase in VL copies/mL was associated with increased odds of cardiovascular risk (Cardiac Risk Score1, β = 0.088, p < 0.01; Cardiac Risk Score2, β = 0.146, p < 0.05). CD4 models were not significant. Conclusion: Our findings demonstrate the independent contribution of detectable VL on cardiovascular risk in YLH. 830 SOLUBLE CD14 IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN SOUTH AFRICAN YOUTH ON ART Sahera Dirajlal-Fargo 1 , Jiao Yu 1 , Abdus Sattar 1 , Sana Mahtab 2 , Jennifer Jao 3 , Landon Myer 2 , Heather Zar 2 , Grace A.McComsey 4 1 Case Western Reserve University, Cleveland, OH, USA, 2 University of Cape Town, Cape Town, South Africa, 3 Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA, 4 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: There is evidence for endothelial dysfunction in youth living with perinatally acquired HIV (YLPHIV). We assessed gut and inflammatory biomarkers associated with endothelial dysfunction in South African YLPHIV. Methods: YLPHIV and age-matched HIV-uninfected (HIV-) youth enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) in South Africa between 9-14 years of age were included. YLPHIV were on ART> 6 months with viral load <400 copies/mL. Endothelial function was measured using reactive hyperemic index (RHI) by Peripheral Arterial Tonometry. Endothelial dysfunction was defined as RHI <1.35. Serum levels of systemic inflammation, monocyte activation, intestinal integrity and oxidized lipids were measured at baseline and 24 months. RHI was measured at 24 months. Spearman correlations were used and quantile regression models assessed associations with RHI. Results: We included 283 YLPHIV and 69 HIV- participants. At baseline, median (Q1, Q3) age was 12 years (11, 13), 53%were females. There was no difference in age, sex or Tanner stages between the groups. At baseline, median CD4 cell count was 744 cells/µL (603, 951). PHIVs had poorer endothelial function compared to HIV- (RHI=1.36 vs 1.52, p<0.01). At baseline and 24 months, YLPHIV had lower BMI but higher waist-to-hip ratio, LDL cholesterol, triglycerides, markers of monocyte activation (sCD14), gut barrier dysfunction (intestinal fatty acid binding protein, IFAB-P) and oxidized LDL cholesterol (p≤0.04). Several biomarkers decreased at 24 months in YLPHIV but remained elevated compared to HIV- (Figure). In univariate analyses, higher levels of IFAB-P at baseline and sCD14 at 24 months correlated with endothelial dysfunction at 24

was calculated at baseline and after 12 months. Statistical comparisons were performed by ANOVA for repeated measures. Results: Mean blood concentration of glucose and HDL cholesterol did not change significantly during the follow-up. Conversely, mean total cholesterol concentration was 190, 159, 161 and 168 mg/dL at baseline, 3, 6 and 12 months, respectively (p = 0.0057). Mean LDL cholesterol values were 109, 90, 92 and 96 mg/dL at baseline, 3, 6 and 12 months (p = 0.025). Mean triglycerides concentration decreased significantly after 3 months of therapy (114 and 64 mg/ dL, p = 0.007). BMI was 20.4 at baseline and 20.9 Kg/m 2 after 12 months (p = 0.09). Body fat percent did not change significantly during the study (p = 0.16), but we observed a remarkable increase in trunk body fat percent (p = 0.0413). In particular, trunk/total body less head (TBLH) fat ratio increased significantly (p = 0.0485), while limbs/trunk fat ratio decreased significantly (p = 0.0495) (Table 1). Conclusion: Our study shows that a dolutegravir-based regimen induces a significant improvement in lipids blood concentration, but no interference on glucose metabolism. On the other hand, we observed a relevant increase in trunk fat without alterations of BMI and body fat percent. Future studies are needed to evaluate if this increase in trunk fat could impact on body metabolism. 828 CHER TRIAL COHORT SHOWS GREATER INSULIN RESISTANCE INTO ADOLESCENCE Claire Davies 1 , Steve Innes 1 , Mark Cotton 1 , Sara H. Browne 2 , Birhanu Ayele 1 1 Stellenbosch University, Tygerberg, South Africa, 2 University of California San Diego, San Diego, CA, USA Background: Few longitudinal studies have examined insulin resistance in HIV-infected children, and of those most have been conducted in developed countries. Our aimwas to examine whether the trajectory of insulin resistance differs in perinatally-HIV-infected children (PHIV) who received early antiretroviral therapy (ART) below 12 weeks of age; HIV-exposed uninfected children (HEU); and HIV-unexposed uninfected children (HU). Methods: This longitudinal cohort study consists of 90 PHIV, 317 well-matched controls (156 HEU and 161 HU) from the same communities and socio-economic background, attending the Family Clinical Research Centre with Ubuntu (FAM- CRU) at Tygerberg Children’s Hospital, South Africa. This cohort was the first to begin ART from below 12 weeks of age with normal CD4 percentages and without clinical HIV disease (CHER trial, Lancet 2013). The cohort has now been followed until 16 years of age. For the present study, children required ≥1 set of simultaneously-obtained fasted serum glucose and insulin measurements. The main outcome was the Homeostatic Model Assessment (HOMA) insulin resistance index (HOMA-IR) (Insulin mIU/L X glucose mg/dL) modelled using log HOMA-IR given skewness. Results: Using linear mixed effects modelling, PHIV had a geometric mean HOMA-IR 1.2 (95% CI 1.1 – 1.3) times above HU (table 1), after adjusting for gender, height (as a surrogate for age, puberty onset and growth), waist circumference (as a surrogate for visceral adiposity), and the random effect of child, given each child had multiple measurements. Elevated HOMA-IR was unlikely linked to differences in environmental or household circumstances in HIV-affected versus -unaffected households, as no significant difference was found between the HOMA-IR of HEU and HU. Conclusion: Despite being closely monitored and on ART since soon after birth, PHIV exhibit elevated insulin resistance that has persisted into adolescence. This has long term implications for cardiovascular risk. Further research needs to identify which PHIV are at risk.

Poster Abstracts

CROI 2020 308