CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: 206 HIV+ children (49.5%male) and 140 controls (55%male) were included in this analysis. HIV+ children were younger than controls (mean age 6.4 ± 1.3 vs 7.2 ± 1.5 years, p<0.01). All HIV+ children were on ART (52% PI-based, 48% NNRTI-based regimens; none receiving tenofovir; mean duration on ART 5.7 ± 1.1 years), 72% had undetectable HIV-1 RNA levels, and median CD4%was 37.7. HIV+ children had lower mean WAZ (-0.8 vs -0.4, p<0.01) and HAZ (-1.4 vs -0.9, p<0.01) than controls. Median SOS was similar between HIV+ and HIV- children (1580 vs 1573, p=0.15). Unadjusted mean BUA was lower in HIV+ than HIV- children (71.5 vs 84.3, p<0.01) and remained lower after adjustment for age, sex, weight, and height (p<0.01). Unadjusted mean SI was also lower in HIV+ than HIV- children (78.5 vs 82.0, p=0.03), remaining lower after adjustment for age, sex, weight, and height (78.6 vs 81.9, p=0.048). Conclusions: In this South African sample of school aged children, lower indices of bone quality by QUS are detectable among HIV+ children receiving ART compared to HIV- controls. QUS may prove to be a valuable method to assess bone quality and acquisition in HIV-infected children in RLS. 933 APOL1 Gene Variants and Chronic Kidney Disease in Perinatally HIV-Infected Youth Murli Purswani 1 ; Kunjal Patel 2 ; CherylWinkler 3 ; Stephen Spector 4 ; Rohan Hazra 5 ; George Seage 2 ; Lynne Mofenson 5 ; Gwendolyn Scott 6 ; RussellVan Dyke 7 ; Jeffrey Kopp 8 For the Pediatric HIV/AIDS Cohort Study (PHACS) 1 Albert Einstein College of Medicine, Bronx, NY, US; 2 Harvard School of Public Health, Boston, MA, US; 3 National Cancer Institute (NCI), Bethesda, MD, US; 4 University of California San Diego, San Diego, CA, US; 5 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, US; 6 University of Miami, Miami, FL, US; 7 Tulane University, New Orleans, LA, US; 8 National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, US Background: Two coding variants, G1 and G2, in the APOL1 gene are present at high frequency in Sub-Saharan African populations. Studies in adults and children have repeatedly demonstrated strong associations between these alleles, operating in a recessive manner, and various glomerular diseases including HIV-associated nephropathy. We explored associations between APOL1 variants and chronic kidney disease (CKD) in youth with perinatal HIV infection (P-HIV). Methods: We carried out a nested case-control study within the PHACS Adolescent Master Protocol, a prospective study of children and youth with P-HIV. Using salivary DNA APOL1 risk alleles (RAs) were genotyped. Race was collected by self-report. Continental ancestry was determined by genotyping 41 ancestry-informative markers and classified as Africa, Europe, America, South/Central, South/West, and East Asia, and Oceania. CKD was defined as ≥ 2 sequential urine protein/creatinine ratios ≥ 0.2 g/g (or dipstick protein ≥ 1+), or ≥ 2 sequential estimated GFRs <60 mL/min/1.73m 2 (Schwartz equation) not followed by a normal value, or a history of disease (nephropathy, nephrotic syndrome, chronic renal failure and focal segmental glomerulosclerosis). P-HIV controls had no evidence of kidney disease. Fisher’s Exact test was used to compare RAs (2 versus 0/1 for G1 combined with G2) by case status using crude odds ratios (OR) and further adjusted for African ancestry (AAnc). Results: Of 448 P-HIV participants, 234 met case/control criteria yielding 27 CKD cases and 207 controls. 70% self-identified as black, 23%white; 41%were male. Mean (area under the curve estimate) HIV viral load difference between cases and controls was 4.07 logs (95% confidence interval [CI]: –1.34 to 7.45). There was a trend for association between self-reported black race and CKD (OR: 3.0; 95% CI: 0.9-10.5). Among blacks carriage of 2 APOL1 RAs was 13%; among whites, none had 2 RAs, but 11% had 1 RA. Further, proportion of AAnc (0.71-0.8) was associated with CKD (OR: 8.8; 95% CI: 1.9-41.4). Association between APOL1 RAs (2 vs 0/1) with CKD was significant in those who self-reported as black (OR: 3.2; 95% CI: 1.2-9.0), and in the overall study population (OR: 4.1; 95% CI: 1.5-11.2). These findings remained significant when adjusted for proportion of AAnc (OR: 3.5, 95% CI: 1.2-10, overall population), suggesting that the APOL1 association is specific for this gene rather than simply tracking AAnc. Conclusions: Carriage of 2 APOL1 risk alleles increases risk for CKD in youth with P-HIV. 934 Cystatin C Is a Marker for Both Inflammation and Renal Function in HIV+ Children Àngela Deyà-Martínez 1 ; Clàudia Fortuny 1 ; Pere Soler-Palacín 2 ; Olaf Neth 3 ; Emilia Sánchez 4 ; Andrea Martín-Nalda 2 ; Lola Falcón-Neyra 3 ; AnnaVila 1 ; AnnaValls 1 ; Antoni Noguera-Julian 1 1 Hospital Sant Joan de Déu, Esplugues, Spain; 2 Hospital Vall d’Hebrón, Barcelona, Spain; 3 Hospital Virgén del Rocío, Sevilla, Spain; 4 Universitat Ramon Llull, BArcelona, Spain Background: Renal toxicity and other non-AIDS conditions are leading causes of morbidity and mortality in HIV-infected adults in the HAART era. Cystatin C has been proposed as a more sensitive marker of renal function in this population, but may be affected by ongoing inflammation. We aimed to study cystatin C levels and how they correlate with classic markers of renal function and inflammatory factors in a cohort of HIV-infected pediatric patients. Methods: Multicentre cross-sectional observational study conducted in a cohort of HIV-infected children and adolescents followed-up in 3 pediatric centers in Spain. Renal function was assessed by means of first morning urine protein/creatinine and albumin/creatinine ratios and creatinine-estimated glomerular filtration rates (eGFR), together with the following inflammatory markers: reactive C protein, beta-2-microglobulin and 25(OH)-vitamin D levels. Plasma cystatin C was measured using a turbidimetric inmunoassay (Multigent cystatin C assay; Abbott Diagnostics, Wiesbaden, Germany; normal values <1.38 mg/L). A control group of sex- and age-matched healthy children and adolescents was used. Results: Overall, 83 HIV-infected patients (51 females, mean age 12.7y) and 49 controls were included. At assessment, mean CD4 cell count was 921/mmcc, 29 patients had a previous AIDS diagnosis, 73 were on HAART (including tenofovir in 28) and HIV viremia was undetectable in 61. No patient presented symptoms consistent with urinary protein loss or renal damage. No differences in renal function and cystatin C levels were observed between patients and controls. In univariate analysis among HIV-infected patients, higher cystatin C levels were associated with no previous AIDS diagnosis (0.89 vs 0.81 mg/L; p=0.05), previous indinavir exposure (1.11 vs 0.87 mg/L; p=0.02), detectable viral load (0.91 vs 0.87 mg/L; p=0.08) and naïve status (0.96 vs 0.87 mg/L; p=0.07). Significant correlations were also observed between cystatin C and eGFR (r=-0.27; p=0.01) and beta-2-microglobulin (r= 0.569; p< 0.01). In multivariate analysis, adjusted by undetectable viremia (yes/no), eGFR (p=0.014), beta-2-microglobulin levels (p=0.001) and prior use of indinavir (p=0.012) remained as independent risk factors for higher cystatin C values. Conclusions: In our study, cystatin C values were associated with eGFR and beta-2-microglobulin. This suggests that cystatin C may be useful as a marker of renal function in HIV- infected pediatric patients, independently of ongoing inflammation or viremia. 935 Cognitive Performance and Intracerebral Findings in Perinatally HIV-Infected Children Sophie Cohen 1 ; MatthanW. Caan 2 ; Jacqueline A. ter Stege 3 ; Henriette J. Scherpbier 1 ;TacoW. Kuijpers 1 ; Peter Reiss 2 ; Gert J. Geurtsen 2 ; Charles B. Majoie 2 ; Ben Schmand 2 ; Dasja Pajkrt 1 1 Emma Children’s Hospital AMC, Amsterdam, Netherlands; 2 Academic Medical Center University of Amsterdam, Amsterdam, Netherlands; 3 Emma Children’s Hospital, Amsterdam, Netherlands Background: Despite the declined incidence of severe neurological complications such as opportunistic infections and HIV-encephalopathy, HIV-infection in children is still associated with a range of cognitive problems. Studies comparing HIV-infected children to socioeconomically (SES) and ethnicity-matched controls are lacking, whereas these are important confounding factors in the context of cognitive functioning. In addition, advanced magnetic resonance imaging (MRI) may serve as a non-invasive tool to gain more insight in the cognitive deficits, and studies using MRI in HIV-infected children are scarce. Methods: HIV-infected children were included from the outpatient clinic of the Emma Children’s Hospital AMC, Amsterdam. Healthy, HIV-unaffected controls were matched to age, gender, ethnicity, and SES. All participants completed a comprehensive neuropsychological assessment (NPA) evaluating intelligence, information processing speed,

Poster Abstracts

560

CROI 2015