CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

ultra high-performance liquid chromatography and tandemmass spectrometry (UHLC/MS/MS2) and gas chromatography/MS. Results: Median age, CD4+ T-cell count, and nadir CD4+ T-cell count were 50y, 373 cells/μl, and 66 cells/μl in the discovery cohort and statistically similar to the validation set. Seventeen (31%; median BDI 32) and 18 (41%; median BDI 23) participants were classified as having high depressive symptoms in the discovery and validation cohort, respectively. Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate (DHEA-S), androstenediols, pregnenolone sulfate) compared to those without depressive symptoms. Cortisol/DHEA-S ratio, an indicator of hypothalamic- pituitary-adrenal axis imbalance, was associated with depressive symptoms due to low DHEA-S (Figure), and discriminated between participants with high vs. low depressive symptoms with AUC of 0.70 (P=0.03, discovery) and 0.80 (P=0.02, validation). When cortisol/DHEA-S was coupled with androstenediol and pregnenolone sulfate, discrimination improved with AUC of 0.81 (discovery) and 0.85 (validation). The odds of having depressive symptoms increased with higher cortisol/DHEA-S ratios [odds 2.5 per z-score, 95% confidence interval 1.3- 4.7], independent of age and gender. Kynurenine to tryptophan ratio showed no significant associations. Conclusion: These findings suggest that altered neuroactive steroid metabolismmay contribute to the pathophysiology of depression in ART- treated HIV-infected adults, representing a potential biological pathway for therapeutic targeting.

(53.0%) and whose current CD4+ T-cell count was >500/µL (54.2%). Median global T-score was 45.8 and median BDI was 12.7. Two hundred fifty-seven (42.3%) took at least one AC drug: The most common were codeine (9.0%), bupropion (8.9%), and trazodone (7.3%). Higher ACB was associated with worse BDI (ρ=0.22, p<0.0001) and global T score (ρ=-0.19, p<0.0001). All seven cognitive domains were affected (p range 0.006 to <0.0001). In multivariable regression models, ACB remained associated with worse BDI (p=0.0001, model R2=0.41, p<0.0001) and trended toward association with global T score (p=0.07, model R2=0.21, p<0.0001). Addition of number of prescribed drugs to models weakened the association of ACB with Global T score below statistical significance (p=0.73) but not with BDI (p=0.003). The AC drugs most strongly associated with BDI were paroxetine, trazodone, atropine, olanzapine, and hydroxyzine. Conclusion: AC drugs are associated with more depressive symptoms, even after accounting for other influential characteristics, including psychiatric diagnoses. This cross-sectional analysis cannot establish causality but eliminating AC drugs frommedication regimens may improve depressive symptoms. 415 ASSOCIATION BETWEEN LUNG AND COGNITIVE DYSFUNCTION IN MEN WITH HIV INFECTION Yoseob J. Hwang 1 , Seyed M. Nouraie 1 , James T. Becker 1 , Dong Chang 2 , Audrey French 3 , Ken M. Kunisaki 4 , Andrew Levine 2 , Eileen Martin 3 , Meredith C. McCormack 5 , Ned Sacktor 5 , Andrea M. Weinstein 1 , Alison Morris 1 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 Rush University, Chicago, IL, USA, 4 University of Minnesota, Minneapolis, MN, USA, 5Johns Hopkins University, Balt imore, MD, USA Background: Lung dysfunction associated with chronic obstructive pulmonary disease (COPD) is common in HIV and a risk factor for developing cognitive dysfunction, a well-recognized comorbidity among persons with HIV infection. We evaluated the relationship between lung and cognitive function in men with and without HIV infection. Methods: We performed a cross sectional analysis of participants in the Multicenter AIDS Cohort Study (MACS). Participants underwent pulmonary function testing including, diffusion capacity for carbon monoxide (DLCO; a measure of oxygen diffusion from the lungs to blood) and forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC; a measure of airway obstruction used to diagnose COPD). The neuropsychological test battery assessed Executive Function, Speed (of information processing), Attention and Working Memory, Learning, Memory, and Motor functional domains. A T score was derived for each functional domain. Multivariable linear regression models estimated the association between the measures of lung and cognitive function. Results: Among 866 participants, 477 (55.1%) had HIV infection. The mean age (standard deviation) of the participants was 55 (12) years. The majority were Caucasian (58.1%). Although a lower DLCO was associated with a lower Executive Function among men without HIV infection (β=0.10; p=0.01), this was not the case among the HIV-infected men (β=0.07; p=0.11). Lower levels of DLCO were associated with lower Speed scores among HIV-infected men (β=0.10; p=0.03), but not among the uninfected men (β=0.00; p=0.91). Among men without HIV infection, a lower FEV1/FVC was associated with reduced Learning (β=19.64; p=0.02) and Memory scores (β=21.63; p=0.01). However, among the HIV-infected men, the associations of FEV1/FVC with Learning (β=8.02; p=0.27) and Memory (β=4.71; p=0.53) did not reach statistical significance. Conclusion: Reduced lung function was associated with poorer cognitive function in the domains of Executive Function, Speed, Learning, and Memory. However, these associations differed by HIV status. appear to be modified by HIV status. Future studies are needed to better elucidate the pathophysiologic mechanisms by which airway obstruction and reduced oxygen diffusion in the lungs interact with HIV status to contribute to cognitive dysfunction.

Poster Abstracts

414 ANTICHOLINERGIC BURDEN IS ASSOCIATED WITH DEPRESSIVE SYMPTOMS IN PERSONS WITH HIV

Asante R. Kamkwalala 1 , Qing Ma 2 , Maile Y. Karris 3 , Erin Sundermann 3 , Ronald J. Ellis 3 , David J. Moore 3 , Leah H. Rubin 1 , Scott L. Letendre 3 1 Johns Hopkins University, Baltimore, MD, USA, 2 University at Buffalo, Buffalo, NY, USA, 3 University of California San Diego, San Diego, CA, USA Background: Persons with HIV (PWH) have a higher risk of depression and neurocognitive (NC) impairment (NCI) than the general population. PWH are also at greater risk for polypharmacy, which increases the risk of adverse events. Many prescribed drugs have anticholinergic (AC) effects, which are a risk factor for depression and NCI in the general population and could contribute to the risk of these conditions in PWH. Methods: To determine the relationships between AC effects and either depressive symptoms or cognitive performance, we analyzed data from 608 PWH on ART who had plasma HIV RNA ≤ 200 copies/mL. AC effects were quantified using the published AC burden (ACB) method. Depressive symptoms were quantified using the Beck Depression Inventory (BDI). Cognitive performance was assessed using a standardized, comprehensive neuropsychological test battery that assessed seven cognitive domains and was summarized by global and domain T scores. Analytical methods included correlation, analysis of variance, and multivariable regression that included demographic, HIV, and ART characteristics as well as medical, psychiatric, and addiction diagnoses. Results: Participants were mostly middle-aged (mean 44.6 years), European ancestry (55.4%) men (85.4%) who had taken ART for more than 4 years

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