CROI 2016 Abstract eBook

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Poster Abstracts

Results: The four infants initiated ART at 2, 2, 2 ½ and 15 months of age respectively and attained sustained viral suppression within 6 months. New-onset neuromotor deterioration was seen at 31, 16, 20 and 53 months of age respectively. Two developed simultaneous language delay at 16 and 20 months respectively. Extensive investigations revealed no alternative aetiology, including ultra-sensitive HIV DNA and RNA PCR on CSF tap performed at 38, 42, 34 and 68 months of age respectively. Magnetic Resonance Imaging revealed generalized cerebral atrophy with extensive periventricular and peritrigonal leukencephalopathy in one child; bilateral mild occipital periventricular hyperintensities in another; and no abnormalities in two children. Slow spontaneous recovery in gross motor and language development was observed over 6 months to 2 years despite no change in ART regimen (see figure). UMN signs resolved far more slowly over 3-5 years. Conclusions: These are the first reported cases of HIVE despite sustained viral suppression in plasma from an early age and undetectable HIV in CSF. Virally-suppressed HIV- infected children remain at risk for HIVE. Slow but complete neuromotor and language recovery is reassuring.

821 A Diffusion Tensor Imaging and Neurocognitive Study of HIV-Infected Children Jacqueline Hoare 1 ; J.P. Fouche 1 ; Nicole Phillips 1 ; John Joska 1 ; Robert Paul 2 ; Kirsten Donald 1 ; KevinThomas 1 ; Dan Stein 1 1 Univ of Cape Town, Cape Town, South Africa; 2 Missouri Inst of Mental Hlth, St. Louis, MO, USA Background: There are no diagnostic criteria for a spectrum of neurocognitive disorders (ND) secondary to HIV infection for children.

Methods: A cross-sectional cohort study was initiated in Cape Town, in which 120 participants, including a HIV negative control group for comparison, completed clinical and neurocognitive assessments. HIV infected children were either stable on antiretroviral treatment (ART) for a minimum of 6 months or ART naïve. Neuroimaging was completed on 105 children in the study. We compared 75 children vertically infected with HIV aged 6 to 16 years, including both children on ART and ART-naïve, with 30 matched controls using diffusion tensor imaging (DTI) measures. We then used the detailed neurocognitive battery; an assessment of adaptive functioning and the American Academy of Neurology (AAN) system for diagnosing HIV associated neurocognitive disorder (HAND) in adults, to establish whether this system could detect a spectrum of ND in HIV infected children. Results: When comparing HIV uninfected children to HIV infected children DTI found damaged neuronal microstructure in the HIV infected children. Significant associations were found between failing first line ART regimen, nutritional-hematological status, HIV-relevant clinical variables, cognitive functioning and white matter integrity in children stable on ART. Children with a clinical diagnosis of encephalopathy (HIVE) had greater white matter damage when compared to children without encephalopathy. DTI also found significant myelin loss in ART naïve children when compared with ART treated children. Using the AAN criteria for HAND we found that 45.35% of the HIV infected children had a ND. ART naïve slow progressors, who receive limited attention from heath care services, as they are thought to be ‘well’, were found to have neurocognitive impairment and white matter microstructural damage. HIV infected children were also more likely to have impaired competence in various domains of functioning. Conclusions: Despite the use of ART and improved virological control with immune reconstitution, there were still a significant percentage of children who were found to have ND. Our findings suggest that children on ART remain at risk for developing CNS disease, and that this risk extends to physically well slow progressors. The HAND criteria designed for adults were able to identify children with functional cognitive impairments who don’t fit criteria for HIVE and would therefore not have been identified otherwise 822 Brain Volumes, HIV Disease Severity, and Substance Use in Perinatally Infected Youth Paige L. Williams 1 ;Yanling Huo 1 ; Shirlene D.Wang 2 ; Kristina Uban 3 ; Kathleen Malee 4 ; Sharon L. Nichols 5 ; Russell B.Van Dyke 6 ; LeiWang 7 ; Elizabeth R. Sowell 8 ; for the Pediatric HIV/ AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) study 1 Harvard Sch of PH, Boston, MA, USA; 2 Northwestern Univ, Chicago, IL, USA; 3 Children’s Hosp of Los Angeles, Los Angeles, CA, USA; 4 Ann and Robert H. Lurie Children’s Hosp of Chicago, Chicago, IL, USA; 5 Univ of California San Diego, San Diego, CA, USA; 6 Tulane Univ Sch of Med, New Orleans, LA, USA; 7 Northwestern Univ, Feinberg Sch of Med, Chicago, IL, USA; 8 Keck Sch of Med at the Univ of Southern California, Los Angeles, CA, USA Background: Combination antiretroviral therapy has improved survival in youth with perinatally-acquired HIV (PHIV), but they remain at risk for poor cognitive outcomes. We compared regional brain volumes of PHIV youth to uninfected controls, and among PHIV youth, evaluated associations with HIV disease severity and substance use. Methods: We conducted structural magnetic resonance imaging (MRI) and cognitive testing in 40 PHIV youth recruited from one site of the PHACS Adolescent Master Protocol study. Current and past HIV disease severity measures were obtained frommedical charts; self-reported substance use indicators were collected using audio computer-assisted structured interviews. Total gray matter and regional brain volumes were generated via FreeSurfer, and compared to 334 control youth from the PING study, adjusting for age and sex. Among PHIV youth, we evaluated associations of HIV disease severity measures and substance use with 11 primary brain volumes using Spearman correlations and via adjusted linear regression analyses. Associations between regional brain volumes and cognitive functioning measures (working memory and processing speed) were also examined. Results: Regional brain volumes were significantly lower for the 40 PHIV youth (mean age=16.7 years) than the 334 PING youth (mean age=16.1 years), with adjusted decreases of 4-10%. Among the 40 PHIV youth, higher peak plasma viral loads showed significant negative correlations with volumes of left and right hemisphere dorsal lateral prefrontal cortex (Spearman r=-0.39 and -0.43) and superior prefrontal cortex (r=-0.35 and -0.35), and with total gray matter (r=-0.35). Youth with recent unsuppressed viral loads (>400 copies/mL, 15%) had significantly lower volumes for these same brain regions (Figure 1); no association with nadir or current CD4 was observed. In adjusted models, youth reporting alcohol use or marijuana use had significantly lower volumes for postcentral gyrus, superior prefrontal cortex, and total grey matter, with decreases ranging from 9-16%. Significant positive associations of total gray matter and other affected brain regions with working memory and processing speed were observed. Conclusions: PHIV youth had significantly lower total gray matter and regional brain volumes than similarly-aged uninfected youth, with largest decreases among PHIV youth with higher viral loads. Alcohol and marijuana use were also linked to lower brain volumes, suggesting that multiple factors may influence brain development.

Poster Abstracts

343

CROI 2016