CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

(CA) in healthy adults. The difference between BA and CA, termed the brain age index (BAI), independently predicts mortality, and is increased by cardiovascular comorbidities and dementia. Here, we assessed BAI in HIV+ compared to matched HIV- adults. Methods: Sleep EEGs from 43 HIV+ adults on ART were gathered and matched to controls (HIV-, n=284) by age, gender, race, alcoholism, smoking and substance use history. We compared BAI between groups and used additional causal interference methods to ensure robustness. Individual EEG features that underlie BA prediction were also compared. Finally, we performed a sub- analysis of BAI between HIV+ with or without a history of AIDS. Results: After matching, mean CA of HIV+ vs HIV- adults were 49 and 48 years, respectively (n.s.). The mean HIV+ BAI was 3.04 years higher than HIV- (4.4 vs 1.4 yr; p=0.048). We found consistent and significant results with alternative causal inference methods. Several EEG features predictive of BA were different in the HIV+ and HIV- cohorts. Most notably, non-REM stage 2 sleep (N2) delta power (1-4Hz) was decreased in HIV+ vs. HIV- adults, while theta (4-8Hz) and alpha (8-12Hz) power were increased. Those with AIDS (n=19, BAI=4.40) did not have significantly different BAI than HIV+ without AIDS (n=23, BAI=5.22). HIV+ subjects had higher rates of insomnia (56% vs 29%, p<0.001), obstructive apnea (47% vs 30%, p=0.03), depression (49% vs 23%, p<0.001), and bipolar disorder (19% vs 4%, p<0.001). Conclusion: HIV+ individuals on ART have excess brain age compared to matched controls using a sleep EEG-based model of brain aging. This excess brain age is partially due to the relative reduction in delta power during N2, suggesting decreased sleep depth in HIV+ subjects. These results suggest sleep EEG could be a valuable brain aging biomarker for the HIV population.

outputs were corrected for T1, T2 relaxation times as well as gray, white and CSF contribution within the MRS voxel of interests. Non-parametric Mann-Whitney and Wilcoxon test were used for comparisons. Results: All 109 participants were male. At baseline, median age (27; range = 18-65), self-reported duration of infection (19 days; range = 3-49), CD4 count (343; range = 101-1302 cells/mm 3 ), and plasma HIV RNA 6.06 (log, copies/mL). In BG, total choline (tCho) and glutamate (Glu) were elevated at M0 compared to HC (p<0.0001) and decreased to HC levels after cART (Figure 1a). Median CD4 count, plasma HIV RNA, and NPZ4 improved significantly with cART. Within the subset of 31 matched individuals, tCho was elevated at M0 (p=0.0002) and remained elevated after 24 months of cART (p=0.048) compared to HC. Baseline levels of WMmyo-inositol (Ins) were similar between groups (HC and M0), but differed at M24, with higher levels observed among AHI compared to M0 (p<0.0001, Figure 1b). Conclusion: This high field (3T) MRS study reveals distinct signatures of neuroinflammation in treatment naïve AHI. (increased tCho and Glu) and after 24 months of cART (increased tCho and Ins). The development of increased Ins after cART suggests the possibility of reactive gliosis despite early cART.

Poster Abstracts

392 LOWER PHYSICAL ACTIVITY AND FITNESS LEVELS ARE ASSOCIATED WITH SMALLER BRAIN VOLUMES Brittany Nelson 1 , Sarah A. Cooley 1 , Dominic Reeds 1 , William T. Cade 1 , Anna

Boerwinkle 1 , Christopher J. Sorensen 1 , Beau Ances 1 1 Washington University in St Louis, St Louis, MO, USA

Background: The average age of people living with HIV (PLWH) is now greater than 50 years. Older PLWH are more sedentary and more frail than similarly aged HIV-seronegative (HIV-) people. Previous studies in HIV- individuals have shown an association between sedentary lifestyle and smaller brain volumes. In this study, we evaluated the relationship between physical activity and fitness levels, and brain volumes in PLWH. Methods: Fifty-six older (>/=50 years old), sedentary (exercise <2 hours a week), virologically controlled (< 50 copies/mL) PLWH underwent 7-day activity monitoring (wrist actigraphy, Actigraph), graded exercise testing on a cycle ergometer (VO2max), structural neuroimaging using MRI, and neuropsychological tests examining multiple domains, including executive function, learning, memory, psychomotor speed and language. We measured the relationship between VO2max, levels of physical activity and nine brain regions commonly affected by HIV (thalamus, caudate, putamen, hippocampus, amygdala, cerebellum, cortical white matter, and total and subcortical gray matter), using partial correlations after correcting for age, race, and sex. Results: By design, subjects were sedentary and spent 89% of the day in sedentary or light activity and only 11% of the day in moderate physical activity. Physical fitness (VO2max , ml/kg/min) was positively correlated with brain volumes including thalamus (p= .009), temporal lobe (p= .025), and total gray matter (p= .017). In addition, actigraphy measures of percent of time spent in sedentary activity also correlated inversely with brain volumes in cortical white matter (p= .025), thalamus (p= .015), caudate (p= .014), and putamen (p= .027). In contrast, we did not observe any significant relationships between VO2max or actigraphy measures of percent sedentary time and neuropsychological performance. Conclusion: These results suggest that lower physical activity within sedentary PLWH is associated with smaller brain volumes (subcortical and cortical).

391 NEUROINFLAMMATION AND REACTIVE GLIOSIS DURING LONG-TERM cART INITIATED IN ACUTE HIV Napapon Sailasuta 1 , Phillip Chan 2 , Carlo Sacdalan 2 , Somporn Tipsuk 2 , Duanghathai Suttichom 2 , Nittaya Phanuphak 2 , Shayanne Martin 3 , Nisakorn Ratnaratorn 2 , Mantana Pothisri 4 , Netsiri Dumrongpisutikul 4 , Jintanat Ananworanich 5 , Victor Valcour 3 , Sandhya Vasan 2 , Serena S. Spudich 6 , Robert Paul 7 1 University of Hawaii at Manoa, Honolulu, HI, USA, 2 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 3 University of California San Francisco, San Francisco, CA, USA, 4 King Chulalongkorn Memorial Hospital, Bangkok, Thailand, 5 Bill and Melinda Gates Foundation, Seattle, WA, USA, 6 Yale University, New Haven, CT, USA, 7 University of Missouri St Louis, St Louis, MO, USA Background: We previously revealed neuroinflammation on magnetic resonance spectroscopy (1.5T MRS) in acute HIV infection (AHI). The aim of this study is to use high field proton MRS (3T MRS) to assess neuroinflammation before and after long-term cART (up to 60 months) initiated during AHI. Methods: Individuals with AHI completed single voxel proton brain MRS on a 3T Phillips MR scanner using standard single voxel double spin echo data acquisition with an echo time of 35ms and a 4-test neuropsychological assessment (NPZ4) before cART (M0, n=109) and at 6 months (M6, n=45), 24 months (M24, n=62) and 60 months (M60, n=25) after cART initiation with sustained viral suppression. A subset of 31 individuals completed both NPZ4 and MRS at M0 and M24. Thai HIV negative participants were included as healthy controls (HC, n=21). Single voxel MRS was acquired from the basal ganglia (BG) and the left frontal white matter (WM) regions. LCModel was used to quantify brain metabolites using GAMMA simulated reference basis sets. The LCModel

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