CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

AZT exposure (β -2.05; 95%CI -3.48, -0.61), and ejection fraction was positively associated with higher proportion of life on ART Conclusion: Nearly one quarter of these children and adolescents demonstrated evidence of early cardiac dysfunction, based primarily on MPI measurements. This finding was associated with older age, higher percentage of detectable HIV RNA, and elevated IL-6 levels. Further investigation is needed into the clinical significance of these findings as abnormal MPI is predictive of mortality in inflammation mediated cardiac dysfunction. 814 WEIGHT IS AN INDEPENDENT RISK FACTOR IN INSULIN RESISTANCE IN HIV+ UGANDAN CHILDREN Sahera Dirajlal-Fargo 1 , Lukasz Weiner 1 , Lingpeng Shan 2 , Manjusha Kulkarni 3 , Christine Karungi 4 , Abdus Sattar 2 , Nicholas Funderburg 3 , Grace Mirembe 5 , Cissy Kityo 4 , Victor Musiime 4 , Grace A. McComsey 6 1 Rainbow Babies and Children’s Hospital–Case Western School of Medicine, Cleveland, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 The Ohio State University, Columbus, OH, USA, 4 Joint Clinical Research Centre, Lubowa, Uganda, 5 Makerere Univ Walter Reed Project, Kampala, Uganda, 6 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: HIV-infection has become a chronic disease in pediatric patients with potential for long-term survival. The risk of cardiometabolic complications in HIV+ and exposed uninfected children (HEU) and their relationship to systemic inflammation is not well established. Our objective was to focus on how insulin resistance is associated with HIV related factors and markers of inflammation, immune activation and gut integrity. Methods: This is a cross-sectional study in HIV+, HEU and HIV unexposed uninfected (HIV-) children aged 2-10 years old enrolled in Uganda. HIV+ children were on stable ART with HIV-1 RNA< 400 copies/mL. Participants were age, body mass index (BMI) and gender matched 1:1:1. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). We measured markers of systemic inflammation, monocyte activation and gut integrity. Kruskal-Wallis tests were used to compare markers by HIV status, and Pearson correlation and multiple linear regressions were used to assess associations of HOMA-IR with biomarkers. Results: Overall, 172 participants were enrolled (57 HIV+, 59 HEU and 56 HIV-). Mean age was 7 years, 55%were females and mean BMI was 15. Among HIV+ children, mean CD4 was 34%, 93% had viral load ≤ 20 copies/mL, 77% were on a non-nucleotide reverse transcriptase regimen. Among traditional cardiovascular disease risk factors, HIV+ participants, compared to HEU and HIV- children, had higher waist hip ratio; HDL cholesterol, triglycerides and levels of HOMA-IR (figure). Four HIV+ participants had insulin resistance (HOMA> 2.5). sCD14, beta d glucan (a marker of fungal translocation) and zonulin (a marker of intestinal permeability) were also higher in the HIV+ group (p≤0.01). Factors associated with HOMA-IR included higher BMI, HDL (r≥0.09, p≤0.01), and lower sTNFRI (r=-0.19, p=0.02). HIV related factors were not associated with HOMA-IR (p≥0.08). After adjusting for age, gender, sTNFRI and family history of diabetes, BMI remained independently associated with HOMA-IR (β=0.14, p<0.01). Conclusion: Despite viral suppression, HIV+ Ugandan children have disturbances in glucose metabolism, immune activation and gut integrity. However, higher BMI, and not immune activation, is associated with insulin resistance in this population. With obesity becoming more frequent in the HIV population, our findings support the need for preventive interventions aimed at weight control in the HIV population, including in children.

1 University of Cape Town, Cape Town, South Africa, 2 Northwestern University, Chicago, IL, USA Background: Evidence in adult populations shows that HIV and antiretroviral therapy (ART) confer cardiovascular (CV) risk. Few studies have assessed endothelial dysfunction (ED), an early marker of subclinical CV risk, in youth living with perinatally acquired HIV (YLPHIV). Methods: Using Peripheral Arterial Tonometry (endoPAT), we compared endothelial function in YLPHIV and age-matched HIV-uninfected (HIV-U) youth enrolled in the Cape Town Adolescent Antiretroviral cohort (CTAAC) in South Africa. A reactive hyperaemic index (RHI) <1.35 was defined as ED. Eligible participants included those aged 9-14 years and on ART >6 months at enrolment. Body mass index z scores (BMIZ) were calculated using WHO references, abnormal lipids were defined as >95th percentile using references from the United States (U.S.) National Health and Nutrition Examination Survey (NHANES), and elevated blood pressure (BP) were defined as >90th percentile for age, sex and height using U.S. standards. Modified Poisson regression models were fit to assess the adjusted association of HIV infection with ED. Subgroup analyses were performed to assess predictors of ED among YLPHIV. Results: Overall 431 YLPHIV and 93 HIV-U youth were included. YLPHIV had lower BMIZ (-0.2 vs 0.4, p<0.01) but higher rates of hypercholesterolemia (10% vs 1%, p=0.01) compared to HIV-U youth. No differences in age, sex, Tanner stage, elevated BP or tobacco use were found. Among YLPHIV, mean log viral load (VL) was 4.83 copies/ml with 21.7% harboring a CD4 count <500cell/ mm3 and median duration on ART was 9.8 years with 38% initiating at <2 years of age. YLPHIV had higher rates of ED compared to HIV-U youth (50% vs 34%, p=0.01); this relationship persisted after adjusting for age, sex, BMIZ, elevated BP, and hypercholesterolemia (RR 1.43, p=0.02). Among YLPHIV CD4 count >500 cell/mm3 (RR 1.04, p=0.76), VL (RR 1.01, p=0.78) and current ART class (protease inhibitor-based vs non-nucleoside inhibitor-based ART, RR 0.90, p=0.186) were not associated with ED after adjusting each model for age, sex, BMIZ, elevated BP, and hypercholesterolemia. Conclusion: Even after adjusting for physiologic differences, YLPHIV appear to be at increased risk for ED compared to age-matched HIV-U youth in South Africa. Further longitudinal studies are required to explore risk of developing CV disease in YLPHIV. AndrewW. McCrary 1 , Winstone Nyandiko 2 , Ibrahim Daud 2 , Elcy Birgen 2 , Joseph Kisslo 1 , Piers Barker 1 , Nathan Thielman 1 , Gerald Bloomfield 1 1 Duke University, Durham, NC, USA, 2 Moi University, Eldoret, Kenya Background: HIV-associated cardiac dysfunction has severe consequences, and traditional measures of echocardiography underestimate the true burden of dysfunction. Novel echocardiographic measures may detect early disease in time for possible intervention. The aims of this study are to define the prevalence of early cardiac dysfunction in children living with HIV and the relationships between cardiac function and same-day HIV RNA and soluble inflammatory marker levels. Methods: Using a cross-sectional study design, perinatally HIV-infected children and adolescent at Moi Teaching and Referral Hospital in Eldoret, Kenya underwent an echocardiogram and provided a blood sample. Early cardiac dysfunction was defined as left ventricular global longitudinal strain (LVGLS) z-score < -2 or myocardial performance index (MPI) ≥ 0.5. Comparisons between those with early cardiac dysfunction and those with normal cardiac function were made using Chi square, Fisher’s Exact, or Wilcoxon Rank Sum tests, as appropriate. Regression models were used to assess the relationship between measures of cardiac function and potential predictors. Results: 643 children and adolescents (mean age 14.1±5.2 years, range 1-25 years) with perinatally acquired HIV were enrolled. The average time on antiretroviral treatment was 6.8±3.6 years. 296 participants (46.0%) had documented exposure to AZT as a part of their treatment regimen. 288 of 638 (45.1%) had detectable HIV RNA levels. 178 of 643 (27.7%) children and adolescents met study criteria for early cardiac dysfunction (176, 98.9%, by the MPI criteria). Early cardiac dysfunction was associated with older age (15.3 vs 13.5 years, p<0.001), higher percentage of detectable HIV RNA levels (52.5% vs 41.7%, p=0.018), and higher median level of plasma IL-6 concentrations (1.00 vs 0.88, p=0.011). In adjusted models, ejection fraction was negatively associated with detectable same-day HIV RNA level (β -0.28; 95%CI -0.56, -0.003) and

Poster Abstracts

813 EARLY CARDIAC DYSFUNCTION IN HIV-INFECTED CHILDREN AND ADOLESCENTS IN WESTERN KENYA

CROI 2019 316