CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: ➢ 135 children were assessed (median age 7.8; IQR 7.6–8.5 years): 84 HIV+ who initiated ART at median 9 (IQR: 7–12) weeks of age; and 51 uninfected (31 HEU + 20 HU) with similar anthrometric Z-scores between groups (p>0.10). ➢ Change in sVCAM-1 and MCP-1, but not sICAM-1, correlated with changes in PWVZ-ht and PWVZ-age in both univariate and adjusted analyses (p<0.05 for all)(see figure 1) Conclusion: ➢ Consistent correlation of sVCAM-1 and MCP-1 with vascular stiffness may indicate the mechanism of premature vascular disease in HIV-affected children. ➢ As overt vascular events are delayed for many years, these chemokines may be useful as early surrogate endpoint biomarkers in prospective research

Poster and Themed Discussion Abstracts

825 VASCULAR HEALTH AND CEREBRAL BLOOD FLOW IN PERINATALLY HIV-INFECTED CHILDREN Charlotte Blokhuis 1 , Sophie Cohen 1 , Henriëtte J. Scherpbier 1 , Henk-Jan M. Mutsaerts 2 , Joost C. Meijers 3 , Neeltje A. Kootstra 2 , Peter Reiss 4 , Ferdinand Wit 4 , Charlotte E. Teunissen 5 , Dasja Pajkrt 1 1 Emma Children’s Hosp/Academic Med Cntr, Amsterdam, Netherlands, 2 Academic Med Cntr, Amsterdam, Netherlands, 3 Sanquin Rsr, Amsterdam, Netherlands, 4 Stichting HIV Monitoring and Academic Med Cntr, Amsterdam, Netherlands, 5 VU Univ Med Cntr, Amsterdam, Netherlands Background: Despite effective virological suppression with cART, children perinatally infected with HIV show neuropsychological dysfunctioning with underlying macro- and microstructural brain injury. The potential role of vascular comorbidity and cerebral blood flow (CBF) in these deficits is unclear. This study aimed to assess whether CBF and vascular disease biomarkers were associated with cerebral and cognitive deficits in HIV-infected children. Methods: This cross-sectional study included 36 cART-treated perinatally infected children aged 8-18 years from the Academic Medical Center in Amsterdam, and 37 age-, sex-, ethnicity- and socio-economic status-matched uninfected controls. We measured markers of inflammation, endothelial activation (using MesoScale Discovery), and coagulation (using enzyme-linked immunosorbent assays) in blood samples from all participants and in cerebrospinal fluid (CSF) from HIV-infected participants. Using 3-Tesla MRI, we determined CBF (using arterial spin labeling), gray matter (GM) volume, white matter (WM) lesion volume, and WM diffusivity (using diffusion tensor imaging). We explored whether CBF and vascular health markers were associated with MRI abnormalities, and cognitive performance (among others intelligence, processing speed, and visuomotor integration) in HIV-infected children using linear and ordered logistic regression analyses. Results: HIV-infected children showed higher CBF in WM, caudate nucleus, putamen, nucleus accumbens and thalamus, as well as higher blood levels of CRP and sVCAM-1. Blood and CSF levels of CRP, sVCAM-1, and sICAM-1 were strongly correlated (Table 1). Higher levels of CRP were associated with higher WMmean diffusivity (blood: coef=2.09; P=.029; CSF: coef=2.27; P=.029), and lower GM CBF was associated with higher WM lesion volume (coef=-0.053; P=.001). Vascular markers were not associated with GM volume, WM lesion volume, or CBF. Among cognitive outcomes, only higher blood sVCAM-1 was strongly associated with poorer visuomotor integration (coef=-17.6; P=<.001). Conclusion: In HIV-infected children, lower GM CBF, and increased inflammation and endothelial activation were associated with WM injury and visuomotor integration. Vascular disease may thus play a role in pediatric HIV-associated cerebral and cognitive deficits. Longitudinal evaluation is warranted to assess whether CBF changes, inflammation and endothelial activation negatively affect white matter health and cognitive performance in this population over time. 826 NEUROPSYCHOLOGICAL OUTCOMES IN A TWO YEAR AFRICAN-BASED PEDIATRIC OBSERVATIONAL STUDY Michael J. Boivin 1 , Miriam Chernoff 2 , Barbara Laughton 3 , Mutsa Bwakura-Dangarembizi 4 , Portia Kamthunzi 5 , Linda Barlow-Mosha 6 , Avy Violari 7 , Mark Cotton 3 , Paul Palumbo 8 , for the IMPAACT P1104s StudyTeam 1 Michigan State Univ, East Lansing, MI, USA, 2 Harvard Univ, Boston, MA, USA, 3 Stellenbosch Univ, Cape Town, South Africa, 4 Univ of Zimbabwe, Harare, Zimbabwe, 5 Univ of North Carolina Proj–Malawi, Lilongwe, Malawi, 6 Makerere Univ–Johns Hopkins Univ Rsr Collab, Kampala, Uganda, 7 Univ of the Witwatersrand, Johannesburg, South Africa, 8 Dartmouth-Hitchcock Med Cntr, Lebanon, NH, USA Background: We compared neuropsychological outcomes over 48 weeks for HIV-infected (HIV), HIV-uninfected perinatally-exposed (HEU), and HIV unexposed (HU) children at 6 sub-Saharan sites. Methods: IMPAACT P1060 compared Nevirapine (NVP) versus Lopinavir/Ritonavir (LPVr)-based ART in HIV-infected children 6 to 35 months of age. P1104s enrolled these children at 5-11 years of age and will evaluate their neuropsychological performance at 3 time points over 2 years, compared to age-matched HEU and HU controls. Evaluation tools included the KABC-II cognitive ability, TOVA attention/impulsivity, BOT-2 motor proficiency tests, and parental BRIEF executive function questionnaires. Cohorts were compared using linear mixed models adjusted for site, child’s age and gender. Personal and social characteristics (child’s growth, development, disability, caregiver’s education and household socio- economic status) were screened (p<0.20) and incorporated in selected analyses. Results: 611 (246 HIV, 183 HEU, 182 HU) of the 615 enrolled at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda) were compared across 2 assessment points (weeks 0 and 48). Mean age at enrollment was 7.2 years, 47%were male, and 69%were in school. 94% of caregivers were biological mothers, 32% had completed high school, 22% received social grants, 38% lived in urban areas, 29% judged family income as sufficient.Unadjusted and adjusted comparisons were consistent. The HIV cohort performed significantly worse than HEU and HU cohorts at both weeks 0 & 48 on KABC-II, TOVA, BOT-2 overall performance (P<0.01), but not on the BRIEF, where the HIV cohort performed similarly or

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