CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

(n=533)) was investigated. For genetic markers with marginally significant association by age interaction (p<0.1), linear regression models were fit to each age group separately. False discovery rate (FDR) was used to adjust for multiple testing. Results: Children with the KIR2DS4*ALL FULL LENGTH ( KIR2DS4*AFL ) allele had higher CD4 + counts vs. those without it (+265 cells; p=0.001). Consistent with these CD4 + findings, children 0-2 years with KIR2DS4*AFL had lower plasma HIV RNA (-0.57log10 copies/ml; p=0.006) and those with KIR2DS4*AFLEX5 had higher cognitive index scores (+5.34; p=0.004). Children 2-18 years with KIR3DS1+Bw4-801 had higher plasma HIV RNA (+0.36log10; p=0.001). These results remained significant after controlling for multiple testing. Other KIR and KIR/HLA alleles with significant associations in univariate analyses, but not after controlling for FDR included: higher HIV RNA in children with KIR2DS2 (0.17log10; p=0.035); higher CD4 + counts in children with KIR3DL1+Bw4 (+204 cells: p=0.006); higher cognitive index scores in children with KIR2DL2*001/2/3/5 (+4.6; p=0.01) and lower cognitive index score with KIR2DL5 in children 2-18 years (-2.95; p=0.038). Conclusions: These data show for the first time that specific KIR alleles independently or combined with HLA ligands affect HIV viral load, CD4 + counts and cognitive index scores of infected, antiretroviral naive children, and these effects appear to be age dependent. These data support a role for specific KIR alleles in HIV pathogenesis.

THURSDAY, FEBRUARY 26, 2015 Session P-U6 Poster Session

Poster Hall

2:30 pm– 4:00 pm Complications of HIV and ART: Pulmonary and Cardiovascular Outcomes 925 Arterial Stiffness in HIV+ Youth and Associations With HIV-Related Variables Allison R. Eckard 1 ; Julia C. Rosebush 1 ; Mary Ann O’Riordan 2 ; ChristopherT. Longenecker 2 ; BridgetWynn 1 ; Monika Uribe Leitz 1 ; Danielle Labbato 2 ; Norma Storer 2 ; Bruce Kinley 2 ; Grace A. McComsey 2 1 Emory University School of Medicine, Atlanta, GA, US; 2 Case Western Reserve University, Cleveland, OH, US Background: Several studies show that HIV+ youth are at an increased cardiovascular disease (CVD) risk as assessed by carotid intima-media thickness (cIMT). Pulse wave velocity (PWV) measures arterial stiffness and is another surrogate measure of CVD risk. Few data exist on PWV in HIV+ youth. Methods: HIV+ youth 8-25 years old on stable ART with an HIV-1 RNA level <1000 copies/mL were prospectively enrolled, along with a group of healthy controls similar in age, sex and race. Carotid-femoral PWV was assessed in triplicate with the SphygmoCor system at a single study visit and averaged (higher PWV = increased arterial stiffness). cIMT, fasting lipids, insulin resistance and CD4 were also measured. We used non-parametric tests and Spearman coefficients to assess differences between groups and correlations with PWV, respectively. Multivariable regression analysis was performed to determine variables independently associated with PWV. Results: 101 HIV+ youth and 86 healthy controls were included. Groups were similar in age, sex and race (HIV+: median (IQR) age = 19 (14, 23) years, 64%male, 89% black). HIV+ group had a median (IQR) HIV & ARV duration of 8 (2, 15) and 3 (1, 10) years, respectively, with a CD4 count of 652 (449, 872) cells/mm 3 . Median (IQR) PWV for the HIV+ group was 5.7 (5.1, 6.2) m/s vs. 5.7 (4.9, 6.5) m/s in controls (P=0.81). In the HIV+ group, PWV was positively correlated with systolic & diastolic blood pressure (BP) (both R=0.3; P<0.01), mean bulb & internal carotid artery IMT (both R=0.3; P ≤ 0.02), male sex (P=0.01), current alcohol use (P<0.01), detectable HIV-1 RNA (P=0.03) and current tenofovir use (P<0.01), and negatively correlated with CD4 count & ARV duration (both R=-0.2; P ≤ 0.04). In the controls, PWV was positively associated with BP (systolic R=0.2; P=0.04; diastolic R=0.3; P<0.01), age (R=0.5; P<0.01), body mass index (BMI) (R=0.4; P<0.01), and current smoking, marijuana and alcohol use (P ≤ 0.04). In multivariable regression, only current alcohol use was independently associated with PWV (P<0.01) in the HIV+ group, whereas, age and BMI were associated with PWV (both P ≤ 0.03) in the controls. Conclusions: This is the largest study of PWV in HIV+ youth to date. There was no difference in PWV between the HIV+ youth and healthy controls. PWV, however, was positively correlated with cIMT in the HIV+ youth, which supports the use of PWV as a measure of CVD risk in this population. Current alcohol use was associated with arterial stiffness, which deserves further investigation. Background: Non-communicable diseases such as atherosclerosis are becoming more important as many HIV+ children on ART are reaching school age. Cross-sectional evidence suggests increased prevalence of vascular disease in children on ART after adjustment for traditional atherosclerosis risk factors. This is associated both with advanced HIV disease and with ART itself (particularly lopinavir/ritonavir, LPVr). Aorto-femoral pulse wave velocity (PWV), a measure of arterial elasticity, predicts incident cardiovascular events in asymptomatic adults and is a gold-standard marker of subclinical atherosclerosis. Previous studies in children have focussed on children initiating ART much later than 3 months of age. Our aimwas to measure PWV in school children who initiated LPVr-based ART before 3 months of age. Methods: Cross-sectional PWV and fasted lipid measurements on primary-school-age children who initiated LPVr-based ART in the CHER trial by 3 months of age, with an existing HIV-uninfected control group from the same communities and socio-economic background. Multivariate linear regression to determine the association between PWV and HIV infection. Results: See table. Unadjusted PWV and growth parameters were similar in the 2 groups. After adjustment for age, gender and body-mass-index-for-age z-score, HIV+ children had adjusted mean total cholesterol 0.7 mmol/L higher than controls (p<0.0001), adjusted mean LDL cholesterol 0.5 mmol/L higher (p=0.001), adjusted mean triglycerides 0.4 mmol/L higher (p<0.0001) and adjusted mean triglyceride to HDL cholesterol ratio 0.3 higher (p<0.0001). However, HIV infection was not associated with differences in PWV after adjustment for age, gender, and systolic blood pressure (p=0.40), despite 80% power to detect a difference as small as 0.3 meters/second. 926 Does Early ART Normalize Pulse-Wave Velocity in Children? Evidence From CHER Cohort Steve Innes 1 ; Zukiswa Magogotya 1 ; Philip Herbst 1 ; Mark F. Cotton 1 ; Barbara Laughton 1 ; Sara Browne 2 ; Richard Haubrich 2 1 Stellenbosch University, Cape Town, South Africa; 2 University of California San Diego, San Deigo, CA, US

Poster Abstracts

555

CROI 2015