CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

with depression (OR=2.69; 95% CI 1.72-4.21) and a trend was observed with being on >1 ACH drug (OR=1.42; 95% CI 0.97-2.09; p=0.07). In a subgroup analysis of patients without depression (N=911), adjusted for age, gender, and polypharmacy, self-reported NCI was associated with the use of >1 ACH drug (OR=1.66; 95% CI 1.08-2.55; p=0.02). Conclusion: ACH drug use is common in elderly PWH and may contribute to self-reported NCI. The effect of ACH drugs on NCI warrants further evaluation using neurocognitive tests. 411 BIOMARKERS OF NUCLEIC ACID OXIDATION AND NEURODEGENERATION IN CSF IN PWH Ronald J. Ellis 1 , David J. Moore 1 , Erin Sundermann 1 , Robert K. Heaton 2 , Todd Hulgan 3 , David C. Samuels 3 , Sanjay R. Mehta 1 , Scott L. Letendre 1 1 University of California San Diego, San Diego, CA, USA, 2 University of California San virologically suppressed individuals, and may contribute to or result from neurodegeneration. 7,8-dihydro-8-oxoguanine (8-oxo-dG), representing oxidatively damaged guanine, is a marker of oxidative DNA damage. Important markers of age-related neurodegeneration include Aβ-42 reduction, reflecting amyloid deposition in brain, and CSF total Tau and neurofilament light (NFL), reflecting neuronal damage. We aimed to examine whether oxidative stress is associated with markers of AD-related neurodegeneration. Methods: Participants were enrolled at six U.S. centers in the CNS HIV Antiretroviral Effects Research (CHARTER) study. Inclusion criteria included HIV RNA ≤50 copies/ml in plasma. Exclusions included significant CNS confounding conditions. Total Tau and Aβ-42 were measured in CSF and plasma by bead suspension array. NFL in CSF and 8-oxo-dG in CSF and plasma were measured using ELISA. Peripheral blood mitochondrial (mt) DNA copy number was obtained from genome-wide genotyping data as a ratio of mtDNA single- nucleotide polymorphism probe intensities relative to nuclear DNA single- nucleotide polymorphisms. Results: Participants were 53 PWH, mean age 55 (+/-9.3), 19%women, 48% non-Hispanic white. Higher 8-oxo-dG correlated with markers of neurodegeneration including lower CSF Aβ-42 (r=-0.34; p=0.012), higher CSF NFL (r=0.39; p=0.0091) and higher total Tau (r=0.6696; p<0.0001). CSF 8-oxo-dG was not related to age, sex, or ethnicity. Aβ-42 was significantly lower in women and African Americans. Higher NFL levels were seen in men and older individuals. Higher total Tau was seen with increasing age. Relationships between 8-oxo and neurodegeneration markers remained after adjusting for demographic variables. 8-oxo-dG was higher among PWH exposed to dideoxynucleoside antiretrovirals. Levels of protein carbonyls, a marker of protein oxidation, were not related to neurodegeneration. Higher 8-oxo-dG, but not protein carbonyls, correlated with lower mtDNA copies per cell (r = -0.59; p = 0.027 and r = -0.31; p = 0.27, respectively). Conclusion: Among virologically suppressed PWH, nucleic acid oxidation was associated with CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, and specific ART drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration. Diego, La Jolla, CA, USA, 3 Vanderbilt University, Nashville, TN, USA Background: Oxidative stress is common in HIV, even among

used to monitor HIV-affected children in resource-constrained settings. Using an automated neurocognitive performance test at one-year of age, we evaluated its predictive validity with neuropsychological performance on validated preschool measures several years later. Methods: 58 uninfected children (25 boys, 33 girls) of mothers with HIV were evaluated at one year of age with the Mullen Scales of Early Learning (MSEL) and the Fagan test of Infant Intelligence (FTII). FTII tests for recognition for pictures of local adult and children faces, usingTobii eye tracking instrumentation to measure gaze direction and duration during successive trials where familiar (previously presented) and novel faces were presented together. After familiarization trials, longer gaze to novel faces is expected. Total screen viewing duration (either face combined) was used as a measure of attention. Most of these children were then tested several years later with the Kaufman Assessment Battery for Children, 2nd Edition (KABC-2) and the visual computerized Tests of Variables of Attention (TOVA). Evaluation took place at the Tororo District Hospital in eastern Uganda. Results: FTII proportion of time viewing novel (vs. familiar) faces was significantly related to overall KABC-2 performance (eta2=0.07), related especially to auditory working memory (KABC Number Recall; p<0.05). FTII proportional preference for novel faces was significantly related to TOVA percent omission errors (vigilance attention). FTII overall attention was related to KABC-2 Hand Movements (eta2=0.11), Rebus (symbol coding learning; eta2=0.13) and TOVA D prime (signal detection; eta2=0.06). MSEL and FTII performance were not significantly related to one another, suggesting they measure different things. MSEL cognitive ability did predict several TOVA performance measures. Conclusion: An eye-tracking based measure of infant measure of attention and working memory (human faces) can predict aspects of neurocognitive performance several years later. Gathering test results automatically, eye tracking-based cognitive assessments in infants can be beneficial in evaluating neurocognitive risk in HIV-infected and affected children; gauging benefits from early treatment and supportive care. We thus provide an innovative performance-based window into the integrity of brain/behaviour development in infancy.

Poster Abstracts

413 LOW NEUROSTEROIDS IDENTIFIES A BIOLOGICAL SUBTYPE OF DEPRESSION IN PEOPLE WITH HIV

Shibani S. Mukerji 1 , Vikas Misra 2 , David Lorenz 2 , Sukrutha Chettimada 2 , Kiana Keller 1 , Scott L. Letendre 3 , Ronald J. Ellis 3 , Susan Morgello 4 , Robert A. Parker 1 , Dana H. Gabuzda 2 1 Massachusetts General Hospital, Boston, MA, USA, 2 Dana–Farber Cancer Institute, Boston, MA, USA, 3 University of California San Diego, San Diego, CA, USA, 4 Mt Sinai School of Medicine, New York, NY, USA Background: The prevalence and mortality risk of depression in people with Human Immunodeficiency Virus infection (PWH) on antiretroviral therapy (ART) is higher than in the general population, yet biomarkers for therapeutic targeting are unknown. Here, we aimed to identify plasma metabolites associated with depressive symptoms in PWH on ART. Methods: This is a prospective study of 99 ART-treated HIV-infected adults (94%with plasma VL < 200 copies/ml) with or without depressive symptoms assessed using the Beck Depression Inventory (BDI) from the NNTC and HNRC cohorts. Participants with BDI scores > 20 were classified as having high depressive symptoms. Plasma metabolite profiles from 55 participants comprised the discovery set; profiles from 44 additional participants were used to validate the accuracy of models. Metabolite profiling was performed using

412 PREDICTIVE VALIDATION OF AN UGANDAN INFANT EYE-TRACKING TEST OF MEMORY OF HUMAN FACES Michael J. Boivin 1 , Itziar Familiar-Lopez 1 , Alla Sikorskii 1 , Ronak Chhaya 1 , Kwabena Nkansah-Amankra 1 , Aatirah Holmes 1 , Jonathan Weiss 1 , Victoria Seffren 2 , Ethan G. Arima 3 , Ojuka J. Caesar 3 , Noeline Nakasujja 4 1 Michigan State University, East Lansing, MI, USA, 2 University of Michigan, Ann Arbor, MI, USA, 3 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 4 Makerere University College of Health Sciences, Kampala, Uganda Background: Neurodevelopmental assessments in early childhood followed by neurocognitive assessments during the preschool-age years are sometimes

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