CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

little data in treated HIV-disease. We sought to build a multivariate model using volumetric neuroimaging data only to accurately predict cognitive function. Methods: T1-weighted neuroimaging data from virally suppressed people living with HIV (PLWH) from the CHARTER cohort (n=139) were segmented into grey and white matter and spatially normalised before entered into machine learning models. Cognitive function was tested across seven cognitive domains with longitudinal decline determined using regression based change scores as previously described. Predictive ability to assess cognitive function was determined using leave-one-out cross validation. Additionally, a multivariate model of brain ageing (training set n=2001, age range 18-90, model R²=0.88) was used to measure the deviation of apparent brain age from chronological age and assess its relationship with cognitive function. Results: Cognitive impairment, defined using the global deficit score (GDS), was present in 37.4%. However, it was generally mild, with only 4.3%meeting the criteria for HIV-associated dementia, and occurred more commonly in PLWH with confounding comorbidities (p<0.001). Longitudinal cognitive decline was present in 14.5%. Although multivariate prediction of cognitive impairment as a dichotomous variable at baseline was poor (table), prediction of the global T-score was better than a comparable linear model (adjusted R2=0.08, p<0.01 vs adjusted R2=0.01, p=0.14). Accurate prediction of longitudinal changes in cognitive function was not possible (p=0.82). Brain-predicted age exceeded chronological age by 1.17 (-0.14-2.53) years, but was greatest in those with confounding comorbidities (5.87 [1.74-9.99] years) and prior AIDS (3.03 [0.00- 6.06] years). The relationship between this deviation and cognitive function was attenuated when covarying for comorbidity status. Conclusion: Although cognitive impairment was present in about a third of virally suppressed patients it was confounded by comorbid conditions. Accurate prediction of cognitive function using multivariate models of T1-weighted MRI data was not achievable, which may reflect the small sample size, heterogeneity of the data or that impairment was usually mild.

studied as healthy controls (HC, n=13). Single voxel MRS was acquired from the basal ganglia (BG) and the left frontal white matter (LFWM). LCModel was used to quantitate brain metabolites using GAMMA simulated reference basis sets. A 4-test neuropsychological battery was performed at all visits. Non-parametric statistical methods were used. Results: At baseline, median age was 29.4 years, mean (Q1, Q3) CD4+ count was 423 (137, 773) cells/mm 3 and log plasma HIV RNA was 6.0. BG GSH was reduced in M60 compared to HC (mean (SD)=4.02(0.19) vs. 5.37(0.41), p=0.02), and reduced in M0 compared to M24 (4.54(0.02) vs 5.53(0.41), p=0.046). In the LFWM, reduced GSH was observed in M0 compared to M6 (3.08 (1.03) vs 3.73(1.5), p=0.05). Pearson correlation was significant between GSH levels at M0 and both a) estimated duration of infection (p=0.033, r=0.33) and b) grooved pegboard performance(p=0.05, r=0.29 (Figure 1)). Conclusion: We report a reduction of cerebral GSH in naïve and treated HIV-infected participants supporting the idea of glutathione metabolism dysfunction and persistent oxidative stress in HIV brain even after early ART. We noted, under our MRS scanning protocol, the two forms of glutathione, the reduced GSH and the oxidized glutathione (GSSG), exhibit very similar proton MRS spectra, therefore glutathione in this study represents total GSH levels. Further study is underway using the novel J-editing method to measure alterations in GSH without GSSG contamination.

Poster Abstracts

437 CEREBRAL GLUTATHIONE METABOLISM IN ACUTE HIV INFECTION AND RESPONSE TO ART Napapon Sailasuta 1 , Jennifer Daniels 2 , Phillip Chan 3 , Carlo Sacdalan 3 , Merlin L. Robb 4 , Somporn Tipsuk 3 , Jintanat Ananworanich 4 , Duanghathai Suttichom 3 , Robert Paul 5 , Nisakorn Ratnaratorn 3 , Mantana Pothisri 6 , Netsiri Dumrongpisutikul 6 , Serena S. Spudich 7 , Victor Valcour 2 1 University of Hawaii at Manoa, Honolulu, HI, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 SEARCH, Bangkok, Thailand, 4 US Military HIV Research Program, Silver Spring, MD, USA, 5 University of Missouri St Louis, St Louis, MO, USA, 6 Chulalongkorn University, Bangkok, Thailand, 7 Yale University, New Haven, CT, USA Background: Oxidative stress, an imbalance between the generation of free reactive oxygen or nitrogen species and body’s ability to neutralize their harmful effects via antioxidants including glutathione (GSH), has been implicated in HIV pathogenesis. Prior studies have reported alteration of blood GSH levels during HIV, but brain GSH levels have never been reported. We measured cerebral total GSH in pre-antiretroviral therapy (ART) acute HIV infection (AHI) and after ART using magnetic resonance spectroscopy (MRS). Methods: 98 Thai AHI participants had single voxel proton brain MRS via a 3T Phillips scanner using standard single voxel double spin echo data acquisition with an echo time of 35ms. Scans were obtained prior to ART at a mean 20 days estimated duration of infection (baseline, M0, n=53), or after six (M6, n=31), 24 (M24, n=18) and 60 (M60, n=9) months of ART started in AHI. 13 participants had scans both at M0 and M6. HIV negative participants were

438 AMYLOID UPTAKE BY PET IMAGING SUGGEST PREMATURE AGING IN OLDER HIV+ INDIVIDUALS Ned Sacktor , Richard Skolasky, Heidi Roosa, Cornelia Demsky, Yun Zhou, Weiguo Ye, Noble George, Peter B. Barker, Dean Wong, Mona Mohamed Johns Hopkins Hospital, Baltimore, MD, USA Background: HIV+ infection leads to pre-mature aging in multiple organ systems. Amyloid deposition, a hallmark of Alzheimer’s disease, can be detected by brain position emission tomography (PET) imaging. The objectives of this study were to determine if amyloid uptake measured by PET [18F] AV-45 (Florbetapir) is increased in older individuals greater than age 50 years: 1) stratified by HIV-associated neurocognitive disorder (HAND) stage among HIV+ individuals, 2) stratified by serostatus, and 3) is increased at an earlier age in HIV+ individuals compared to HIV- individuals. Methods: 43 HIV+ and 23 HIV- individuals received neurological evaluations including neuropsychological testing, functional assessments and high resolution research tomography (HRRT) PET [18F] AV-45 imaging. AV-45 uptake was measured by cerebellum standardized uptake value ratios (SUVR) in 17 cortical and subcortical regions. Global and regional cortical uptake were compared 1) by HAND stage (among HIV+’s only), 2) by serostatus (entire cohort), and 3) stratified by age decade comparing individuals in their 50’s, 60’s and 70’s by serostatus. Results: Age decade for HIV+ individuals were 50’s (n =22), 60’s (n=20), and 70’s (n=1), and for HIV-’s: 50’s (n=6), 60’s (n=10), and 70’s (n=7). HAND stage

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