CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

RNA of 106,250 (IQR, 13,570-218,250) and 2327 (IQR, 49-70,550) cp/mL. A total of 146 and 312 metabolites have been identified respectively in CSF and plasma, grouped in 19 and 23 different metabolic pathways. Significant differences were identified in molecules involved in glutamate, biliary acids and fatty acid metabolism. Table displays metabolic pathways found to have >1 molecule showing a fold change of HAD vs. ASYM>1.5 or < 0.5, either in CSF or plasma. Conclusion: HAD untreated patients show a perturbation in glutamate, bile acids and fatty acids homeostasis, which may result from impaired cell metabolism induced by HIV both systemically and in the central nervous system. The increased production of compounds possibly exerting neurotoxic effects, such as glutamate, 5-oxoproline and primary bile acids, might contribute to the neuronal damage and foster neurological impairment in HAD. On the other hand, changes in lipid metabolismmay reflect both an enhanced adipose reserves’ breakdown and mitochondrial dysfunction with impairment in β-oxidation. These markers, tested in untreated patients, may have a potential for the identification and studying the pathogenesis of HIV-mediated neuronal damage also in cART treated patients.

fully adjusted models. Among HIV+ women, associations of executive function, psychomotor speed, and motor skills were attenuated and no longer significant after adjustment for demographic and comorbid conditions (Table). Among HIV- women, impaired executive function and motor skills were associated in unadjusted models and the associations were strengthened in fully adjusted models. Conclusion: NC impairment in executive function, psychomotor speed, and motor skills domains is associated with falls among women in the WIHS cohort. Among HIV+ women, associations between NC impairment and falls were no longer significant after adjustment for demographics and comorbid conditions, whereas in HIV- women, the associations were strengthened after adjustment, suggesting that these relationships may be modified by different factors. Additional studies are needed to understand mechanisms by which domain- specific NC impairment impacts fall risk, and whether cognitive interventions can reduce falls among aging women with or without HIV.

Poster Abstracts

425 HIV-ASSOCIATED NEUROCOGNITIVE DISORDER LEADS TO DEATH

Deanna Saylor 1 , Gertrude Nakigozi 2 , Noeline Nakasujja 3 , Alice Kisakye 2 , Aggrey Anok 2 , Richard Mayanja 2 , James Batte 2 , Kevin Robertson 4 , Ronald H. Gray 5 , Maria Wawer 5 , Ned Sacktor 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Rakai Health Sciences Program, Kalisizo, Uganda, 3 Makerere University College of Health Sciences, Kampala, Uganda, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: Neurocognitive impairment has been associated with increased mortality in both antiretroviral therapy (ART)-treated and ART-naïve populations. However, mortality risk associated with specific HAND stages (i.e. normal, asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), and HIV-associated dementia (HAD)) has not been assessed. Moreover, there is current debate regarding the clinical significance of ANI. Methods: 399 HIV+ ART-naïve participants in rural Rakai, Uganda were assessed with a neuromedical examination, neuropsychological test battery, depression screening, and functional status assessments, and a HAND stage was assigned based on Frascati criteria. All participants were immediately offered ART. After two years and again after 5 years, participants were traced with phone calls and, if unreachable, through a proxy phone contact and/or study personnel home visits to confirm vital status. Those unable to be traced were classified as lost to follow-up (LTFU). Logistic regression analyses were used to assess the relationship between baseline HAND stage and two-year and five- year all-cause mortality. Results: At baseline, participants’ mean age was 35 (SD 8) years, 53% were male, and mean years of education was 5 (SD 3). After two years, 337 participants (84%) were alive, 17 (4%) were confirmed dead, and 45 (11%) were LTFU. After five years, 157 participants (39%) were alive, 20 (5%) were dead, and 222 (56%) were LTFU. Omitting those LTFU, every one-stage increase in baseline HAND severity was associated with a 68% increased odds of death at two years and 96% increased odds of death at 5 years (Table). There was a trend for a dose-dependent increased odds of death for each HAND stage compared to participants with normal cognition at both two and five years. In multivariate analyses controlling for baseline CD4 count and demographic factors, each one-stage increase in HAND severity was associated with a 58% increased odds of death at two years, which was borderline significant [OR 1.58, 95%CI (0.97, 2.57), p=0.06], and 83% increased odds of death at 5 years [OR 1.83, 95%CI (1.13, 2.96), p=0.01] (Table).

424 IMPAIRED COGNITION PREDICTS FALLS AMONG HIV+ AND HIV- WOMEN Anjali Sharma 1 , David Vance 2 , Donald R. Hoover 3 , Qiuhu Shi 4 , Michael T. Yin 5 , Susan Holman 6 , Michael Plankey 7 , Phyllis Tien 8 , Kathleen M. Weber 9 , Michelle Floris-Moore 10 , Hector Bolivar 11 , Elizabeth T. Golub 12 , Marica M. Holstad 13 , Leah H. Rubin 14 , for the Women’s Interagency HIV Study 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 University of Alabama at Birmingham, Birmingham, AL, USA, 3 Rutgers University, Piscataway, NJ, USA, 4 New York Medical College, Valhalla, NY, USA, 5 Columbia University Medical Center, New York, NY, USA, 6 SUNY Downstate Medical Center, Brooklyn, NY, USA, 7 Georgetown University, Washington, DC, USA, 8 University of California San Francisco, San Francisco, CA, USA, 9 Cook County Health & Hospitals System, Chicago, IL, USA, 10 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 11 University of Miami, Miami, FL, USA, 12 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 13 Emory University, Atlanta, GA, USA, 14 Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Emerging evidence suggests that objectively assessed neurocognitive (NC) function in the domains of psychomotor speed, attention, and executive function are strong predictors of falls in older adults. Domain- specific NC impairments may be stronger predictors of fall risk in HIV+ compared to HIV- women. Methods: We analyzed data from 825 HIV+ and 392 HIV- women in the Women’s Interagency HIV Study (WIHS) who underwent NC testing within two years prior to completing a self-reported falls survey. The primary exposure variables of interest were NC impairment (T score <40) on each of 7 domains: executive function, psychomotor speed, attention, learning, memory, fluency, and fine motor skills. For NC domains associated with falls in simple logistic regression (p<.05), hierarchical regression models evaluated associations between NC impairment and odds of any fall in the prior 6 months after adjusting for: (1) study site and HIV status (2) demographics, (3) comorbid conditions, (4) substance use/CNS active medications, and HIV-specific factors. Results: Median age was higher in HIV+ than HIV- women (51yrs vs. 48yrs, p <0.0001); the 6-month prevalence of falls (18%) did not differ by HIV. In the overall sample, executive function (odds ratio, OR:1.82;95%CI:1.21-2.74;p= 0.004), psychomotor speed (OR:1.59;95%CI:1.05-2.42;p= 0.03), and motor skills (OR:1.70;95%CI:1.11-2.61;p=0.02) were associated with greater odds of falls in

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