CROI 2020 Abstract eBook
Additional investigation of inflammatory events during acute HIV infection could offer key information on longitudinal neurological outcomes.
negative persons. Previously we described ACH use in PWH >65 years old in the Swiss HIV Cohort Study (SHCS) and the association with self-reported NCI using SHCS screening questions for memory, attention, and reasoning difficulties. The current study aimed to further assess the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent detailed neuropsychological evaluation using a standardized testing battery. Methods: A medication reviewwas performed in PWH >45 years old enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort (NAMACO), a sub-cohort of the SHCS. NAMACO participants were included regardless of self-reported NCI. Neurocognitive function was evaluated for 7 domains by trained neuropsychologists. Binary outcomes (presence/absence of impairment) were assessed for each individual domain and combined to determine overall neurocognitive function. The effect of ACH and sedative drugs on neurocognitive function was evaluated using multivariable logistic regression models adjusted for patient demographic characteristics, HIV history, comorbidities, illicit substance use, alcohol binge and efavirenz/dolutegravir use. Results: 963 PWH (80%male, 92% Caucasian, 96% virologically suppressed, median age 52 [IQR: 49-57]) were included. 16% of participants were prescribed >1 sedative drug and 14%>1 ACH drug, with 82% of these drugs having an ACH activity score <3. 41% of participants had NCI, mainly related to impairment of motor domain. Sedative drugs were associated with impairment of attention and verbal learning domains (OR 1.98; 95% CI 1.28-3.07; and OR 1.77; 95% CI 1.07-2.93), and ACH drugs with impairment of motor and sensory skills domains (OR 1.71; 95% CI 1.08-2.71; and OR 3.09; 95% CI 1.43-6.66). Increased risk of overall NCI was associated with sedative drugs (OR 1.55; 95% CI 1.00-2.40; p=0.048) and was borderline for ACH drugs (OR 1.58; 95% CI 0.98-2.55; p=0.06). Other significant associations with overall NCI were older age, lower education and being non-Caucasian. Conclusion: Non-HIV drugs can contribute to NCI with sedative drugs altering attention and learning functions and ACH drugs impairing motor and sensory functions. HIV clinicians need to consider these drugs when assessing NCI. 410 ANTICHOLINERGIC DRUG USE IN PATIENTS ≥ 65 YEARS OLD IN THE SWISS HIV COHORT STUDY Bernadette Jakeman 1, Alexandra Scherrer 2 , Huldrych F. Günthard 3 , Matthias Cavassini 4 , Anna Hachfeld 5 , Alexandra Calmy 6 , Patrick Schmid 7 , Enos Bernasconi 8 , Manuel Battegay 9 , Catia Marzolini 9 , for the Swiss HIV Cohort Study 1 University of NewMexico College, Albuquerque, NM, USA, 2 University of Zurich, Zurich, Switzerland, 3 University Hospital Zurich, Zurich, Switzerland, 4 University of Lausanne, Lausanne, Switzerland, 5 University Hospital of Bern, Bern, Switzerland, 6 University Hospitals of Geneva, Geneva, Switzerland, 7 St. Gallen Cantonal Hospital, St. Gallen, Switzerland, 8 Servizio di Malattie Infettive, Lugano, Switzerland, 9 University Hospital Basel, Basel, Switzerland Background: Medications with anticholinergic (ACH) activity have been associated with neurocognitive impairment (NCI), particularly in elderly due to a reduced number of cholinergic receptors. People with HIV (PWH) are more likely to have NCI as they age. Additional risk factors include viral replication, chronic inflammation, antiretroviral therapy (ART) toxicity, higher rates of depression, and previous central nervous (CNS) infections, making this population especially vulnerable to ACH effects. This study determined the prevalence of prescribed ACH drugs and their association with self-reported NCI in elderly PWH of the Swiss HIV Cohort Study (SHCS). Methods: A literature review was performed to identify ACH drugs with documented ACH activity, supporting side effect profile, and CNS penetration. The degree of ACH activity was scored from 0 to 3, a higher score indicating more ACH activity. A medication review was performed in July 2019 for all SHCS participants >65 years old to assess the prevalence of prescribed medications with ACH properties. Association between ACH burden and neurocognitive complaints was evaluated using the SHCS self-reported NCI questions addressing memory loss, attention difficulties, and slowing of reasoning ability. Results: 1019 PWH (82%male) with a median age of 70 [IQR: 67-74] years were included. Most patients were on ART (99%); 50.8%were integrase inhibitor regimens. The average number of non-HIV drugs was 5.1+3.6, representing a polypharmacy (i.e. >5 non-HIV drugs) prevalence of 50.2%. 200 participants (19.6%) were on >1 drug with ACH activity, with an average ACH score of 1.7. Overall, 131, 22 and 46 PWH had an ACH score of 1, 2 and >3, respectively. Antidepressants were the most prescribed ACH drugs (49.8%). Gender and age were not associated with ACH drug use however polypharmacy was (p<0.001). Self-reported NCI, adjusted for age, gender, and polypharmacy was associated
408 PROTEOMIC CHARACTERIZATION OF CSF EXTRACELLULAR VESICLES IN HIV PATIENTS Debjani Guha 1 , David Lorenz 1 , Vikas Misra 1 , Sukrutha Chettimada 1 , Susan Morgello 2 , Dana H. Gabuzda 1 1 Dana–Farber Cancer Institute, Boston, MA, USA, 2 Mt Sinai School of Medicine, New York, NY, USA Background: Extracellular vesicles (EVs) are nano-sized particles present in most body fluids including cerebrospinal fluid (CSF). Little is known about CSF EV proteins in HIV+ individuals. In this cross-sectional study, we characterized the CSF EV proteome in HIV+ subjects and its relationship to neuroinflammation, stress responses, and HIV-associated neurocognitive disorders (HAND). Methods: CSF EVs isolated from 20 age-matched HIV+ subjects with (n=10) or without (n=10) cognitive impairment were characterized by electron microscopy, nanoparticle tracking analysis, immunoblotting, and untargeted LC/MS/MS mass spectrometry. Functional annotation was performed by gene ontology (GO) mapping and expression annotation using Biobase Transfac and PANTHER software. Cultured astrocytic U87 cells were treated with hydrogen peroxide for 4 hours to induce oxidative stress and EVs isolated by ultracentrifugation. Selected markers of astrocytes (GFAP, GLUL), inflammation (CRP), and stress responses (PRDX2, PARK7, HSP70) were evaluated in EVs released by U87 cells following induction of oxidative stress, and in CSF EVs from HIV+ patients by immunoblotting. Results: Mass spectrometry identified 2727 and 1626 proteins in EV fractions and EV-depleted CSF samples, respectively. CSF EV fractions were enriched with exosomal markers including Alix, syntenin, tetraspanins, and heat-shock proteins, and a subset of neuronal (ENO2, NFL, NPTN, NRXNs), astrocyte (GFAP, PEA15, S100B, SLC1A3), oligodendrocyte (MAG, MBP, MOG), and choroid plexus (ACO2, CLIC6, COMT, EZR, TTR) markers in comparison to EV-depleted CSF. Proteins related to synapses, immune/inflammatory responses, stress responses, metabolic processes, mitochondrial functions, and blood-brain barrier were also identified in CSF EV fractions by GO mapping. HAND subjects had higher abundance of CSF EVs (p<0.005) and proteins mapping to GO terms for synapses, glial cells, inflammation, and stress responses compared to those without HAND. GFAP, GLUL, CRP, PRDX2, PARK7, and HSP70 were confirmed by immunoblotting of CSF EVs of HAND subjects and were also detected in EVs released by U87 cells under oxidative stress. Conclusion: CSF EVs derived from neurons, glial cells, and choroid plexus carry synaptic, immune/inflammation-related, and stress response proteins in HIV+ individuals with cognitive impairment, representing a valuable source for biomarker discovery. 409 EFFECT OF NON-HIV DRUGS ON NEUROCOGNITIVE DOMAINS IN A WELL- TREATED HIV POPULATION Bernadette Jakeman 1 , Alexandra Scherrer 2 , Katharine Darling 3 , Isaure Nadin 4 , Barbara Hasse 2 , Christoph Hauser 5 , Philip E. Tarr 6 , Alexandra Calmy 4 , Ursula Kunze 7 , Marcel Stoeckle 8 , Patrick Schmid 9 , Manuel Battegay 8 , Renaud Du Pasquier 10 , Matthias Cavassini 10 , Catia Marzolini 8 1 University of NewMexico, Albuquerque, NM, USA, 2 University Hospital Zurich, Zurich, Switzerland, 3 Lausanne University Hospital, Lausanne, Switzerland, 4 University Hospitals of Geneva, Geneva, Switzerland, 5 University Hospital of Bern, Bern, Switzerland, 6 Kantonsspital Baselland, Bruderholz, Switzerland, 7 Memory Clinic Felix Platter Spital, Basel, Switzerland, 8 University Hospital Basel, Basel, Switzerland, 9 St. Gallen Cantonal Hospital, St Gallen, Switzerland, 10 University of Lausanne, Lausanne, Switzerland Background: Neurocognitive impairment (NCI) remains a problem in people with HIV (PWH) despite advances in HIV management. Medications with anticholinergic (ACH) activity have been associated with NCI in aging, HIV-
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