CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

414 CLUSTER ANALYSIS OF COGNITIVE FUNCTIONING IN HIV+ AND HIV- SUBJECTS Lillian Ham 1 , Joseph Snow 1 , Brian K. Agan 2 , Bryan Smith 1 , Avindra Nath 1 , Seung Hyun Won 3 , Xiuping Chu 3 , Elizabeth F. Horne 1 , Gina Norato 1 , Tracyann Mburu 1 , for the Neuro-HIV Research Consortium 1 NIH, Bethesda, MD, USA, 2 Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 3 Henry M Jackson Foundation, Bethesda, MD, USA Background: Although several definitions have been proposed to define HIV-associated neurocognitive disorders, no universally accepted definition has emerged. Previous investigations have employed cluster analyses (CA) to identify neurocognitive performance subgroups among HIV patients. However, no previous studies have included both HIV+ and HIV- subjects in such CAs. Methods: Baseline visits of 324 HIV+ and HIV- subjects (M age =50.4; 245 males; 47.8% Black, 44.8%White, 23% Other) who underwent comprehensive neuropsychological assessment were included. HIV+ and HIV- subjects did not differ in age, gender, or race (ps>.13), but controls were more educated (p<.01). In the first of a two-stage CA, 15 measures of attention, executive functioning, information processing, verbal fluency, learning, psychomotor, and memory that are commonly used to assess HAND were entered into a hierarchical CA, in which two clusters were identified. Group membership was finalized through a k-means CA which produced two groups defined as low or high performing. Out of 96 controls, 40 (41.7%) were classified as low performing and 56 (58.3%) were high performing. Out of 228 HIV+ subjects, 120 (52.6%) were classified as low performing and 108 (47.4%) were high performing. Results: The two clusters were compared to cognitive impairment (CI) based on Global Deficit Score (GDS; ≥0.5). In comparison to CI, the CA had high sensitivity (100%) but low specificity (62.1%). Chi-square analyses found that the low performers were characterized by lower employment (p<.01), more PTSD (p=.03), higher rate of current smokers (p<.01), and more individuals taking psychiatric medication (p<.01). Mann-Whitney tests also found that the low performers endorsed more symptoms of depression (Beck Depression Inventory; p<.01), lower premorbid IQ (Wechsler Test of Adult Reading; p<.01), and lower everyday functioning (Texas Functional Living Scale; p<.01). As expected, the low performers had significantly lower GDS (p<.01) and overall T-scores on cognitive measures (p<.01). Low and high performers did not differ in HIV status (p=.07), education (p=.38) or age (p=.64). Conclusion: Using CA on neuropsychological performance of HIV+ and HIV- subjects, we identified low and high cognitive performers. We concluded that cognitive impairment is not HIV-status specific. Other psychiatric, health, and functional characteristics had stronger associations with cognitive performance than HIV status did.

Poster Abstracts

415 ALZHEIMER’S DEMENTIA CEREBROSPINAL FLUID BIOMARKERS IN HIV- POSITIVE PATIENTS ON cART Mattia Trunfio 1 , Caterina Martini 2 , Lorenzo Mighetto 2 , Daniela Vai 2 , Daniele Imperiale 2 , Stefano Bonora 1 , Giovanni Di Perri 1 , Andrea Calcagno 1 1 University of Torino, Torino, Italy, 2 Maria Vittoria Hospital, Torino, Italy Background: Evidence regarding cerebrospinal fluid (CSF) Alzheimer’s dementia (AD) biomarkers in HIV-positive patients is conflicting. The study aimed to describe total tau (tTau), phosphorylated tau (ptau) and β Amyloid 1-42 (βA42) CSF concentrations and clinical correlates among on cART HIV- positive patients Methods: On cART HIV-positive adults undergoing lumbar puncture for clinical reasons were enrolled and divided into 4 groups by CSF age-adjusted tTau and βA42 cut-offs: A (both normal), B (normal tTau, low βA42), C (high tTau, normal βA42), D (both altered). CSF biomarkers were measured by immune-enzymatic (tTau, ptau, βA42), ELISA (neopterin) and immunoturbidimetric (CSF-serum albumin ratio [CSAR], CSF IgG synthesis) methods. Data were analysed through non-parametric tests Results: 181 patients were included: 150 (82.9%), 15 (8.3%) and 15 (8.3%) resulted in group A (CSF tTau 116 [51-199], βA42 899 [788-1079] pg/mL), B (CSF tTau 37 [37-128], βA42 374 [302-443] pg/mL) and C (CSF tTau 544 [466- 750], βA42 965 [754-1267] pg/mL). Only 1 patient was in group D (tTau 580 and βA42 404 pg/mL) and was diagnosed with AD. Demographic, clinical, viroimmunological and CSF variables are shown in the Table. CSF tTau positively correlated with CSF ptau (.68, p<.01), βA42 (.48, p<.01), neopterin (.43, p<.01), and PBMC HIV-DNA (.44, p.012). Higher CSF tTau levels were associated with worse score at verbal long and short-termmemory tests (-.41 and -.42, p.027 and p.024). CSF βA42 positively correlated with CSF ptau (.62, p<.01) and working memory task (.78, p<.01). Compared to group A, group B presented higher CSF neopterin (p<.01), cells (p.<01), proteins (p.04), IgG synthesis (p.01) and Tourtelotte index (p<.01) and showed wider proportion of non-caucasian ethnicities and past iv drug use (p<.01 and .03) and higher risk of having altered brain MRI (OR 16.3, p.05) and executive functioning task (OR 45.0, p.02) Conclusion: In HIV-positive patients on cART, CSF tTau and βA42 resulted to be informative of different stages of CNS involvement by HIV and were associated differently fromwhat is observed in AD. While elevated CSF tTau related to recent infection, poor viral control and/or CNS opportunistic infections, low CSF βA42 levels featured a small subgroup of patients with ongoing intrathecal synthesis and CNS inflammation/immune activation despite effective and long- term peripheral viral suppression. Longitudinal studies assessing evolution or persistence of such CSF patterns are warranted.

CROI 2019 150