CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

422 SCD14, SICAM-1, AND SVCAM-1 CORRELATE WITH NEUROCOGNITIVE FUNCTION IN YOUTH WITH HIV Julie J. Kim-Chang 1 , Matthew S. Loop 2 , Kevin Donovan 2 , Suzi Hong 3 , Bernard Fischer 1 , Guglielmo Venturi 1 , Patricia A. Garvie 4 , Jordan Kohn 3 , H. Jonathon Rendina 5 , Steven P. Woods 6 , Maureen Goodenow 7 , Sharon Nichols 3 , John W. Sleasman 1 , for the Adolescent Medicine Trials Network (ATN) for HIV/ AIDS Interventions 1 Duke University School of Medicine, Durham, NC, USA, 2 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3 University of California San Diego, La Jolla, CA, USA, 4 Children’s Diagnostic & Treatment Center, Fort Lauderdale, FL, USA, 5 Hunter College, CUNY, New York, NY, USA, 6 University of Houston, Houston, TX, USA, 7 NIH, Bethesda, MD, USA Background: HIV infection affects cognitive performance through immune activation and related mechanisms. We hypothesized that in youth with HIV (YWH), biomarkers of macrophage activation and vascular injury are associated with impairment in distinct neurocognitive domains. Methods: YWH, ages 20 to 28, enrolled in ATN 071/101 were assessed for biomarkers of macrophage activation and vascular injury using ELISA/ multiplex assays. Participants completed standardized neurocognitive tests. Demographically corrected z-scores were combined to form indices of attention, motor functioning, executive functioning, and both verbal and nonverbal memory. We performed a cross sectional analysis of the relationship between blood levels of four key biomarkers (sCD163, sCD14, sICAM-1, and sVCAM-1) and performance in each of these neurocognitive domains. Linear regression models were fit for the log-transformed biomarker value for each combination of biomarker and cognitive domain score. These models were adjusted for demographics, socioeconomic status, substance use, and depression. Results: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86%male, 68% African American]. We found moderate evidence for the following associations: sCD14 was negatively associated with executive function [adjusted estimate -0.69 (95% CI -1.43, 0.05)] and non-verbal memory [-0.99 (-1.89, -0.10)]. Soluble ICAM-1 was negatively associated with verbal memory [-0.31 (-0.64, 0.03)], while sVCAM-1 was positively associated with attention [0.32 (-0.04, 0.69)], executive function [0.68 (0.29, 1.08)], and non-verbal memory [0.56 (0.04, 1.07)]. Soluble CD163 was not significantly associated with any domain. None of the key biomarkers were significantly associated with the motor domain. Conclusion: Biomarkers of macrophage activation and vascular injury were differentially associated with distinct cognitive domains, especially executive function and memory, among YWH. Intriguing positive associations of soluble VCAM-1 with executive function and nonverbal memory may indicate a link between vascular flow and cognitive performance among YWH who are at early stage of disease. 423 METABOLOMIC PROFILING OF HIV PATIENTS WITH AND WITHOUT HIV- ASSOCIATED DEMENTIA Andrea Mastrangelo 1 , Magnus Gisslén 2 , Richard W. Price 3 , Filippo Turrini 1 , Roberta Caccia 1 , Leonid Gorelik 4 , Bestetti Arabella 1 , Adriano Lazzarin 1 , Cinque Paola 1 1 San Raffaele Scientific Institute, Milan, Italy, 2 University of Gothenburg, Gothenburg, Sweden, 3 University of California San Francisco, San Francisco, CA, USA, 4 Fortress Biotech, Waltham, MA, USA Background: HIV-associated dementia (HAD) is the most important clinical expression of HIV-mediated neurotoxicity, and even though cART has lowered its incidence, HIV-related neurocognitive disorders remain a major issue. The exact mechanism explaining the neurological decline observed in HIV-infected patients is still only partly understood. Thus, we have exploited metabolomics as a new approach to detect novel biomarkers of HAD among the small molecules of both cerebrospinal fluid (CSF) and plasma. Methods: Metabolomics was performed in paired CSF and plasma samples of 20 untreated patients with HAD, 20 HIV-infected, neurologically asymptomatic patients (ASYM) and 20 HIV negative controls (NEG) by Metabolon (Durham, NC) using both liquid and gas chromatography/mass spectrometry. Molecules were identified by comparison to library entries or purified standards and analysed by Welch’s two samples t-test. Differences with a p value <0.05 and a q value <0.1 were considered significant. Results: HAD and ASYM had, respectively, a median CD4+ cell count of 22 (IQR, 3-148) and 151 (IQR, 91-261) cells/mm3, a median plasma HIV RNA of 202,000 (IQR, 53,000-679,500) and 22,424 (IQR, 711-70,550) cp/mL and a median CSF HIV

421 ASSOCIATION BETWEEN NEUROFILAMENT LIGHT PROTEIN AND IMPAIRED COGNITION IN TREATED HIV

Elizabeth F. Horne 1 , Ulisses Santamaria 1 , Ankit Saxena 2 , Edmund C. Tramont 3 , Stanley Rapoport 4 , Joseph Snow 4 , Chuen-Yen Lau 3 , John P. McCoy 2 , Avindra Nath 1 , Bryan Smith 1 , for the Neuro-HIV Consortium 1 National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA, 2 National Heart, Lung, and Blood Institute, Bethesda, MD, USA, 3 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 4 NIH, Bethesda, MD, USA Background: Neurofilament light protein (NFL) concentrations in CSF can be used as sensitive biomarkers to evaluate CNS injury and dysfunction. Elevated NFL has been associated with CNS dysfunction in untreated HIV infection. This study investigates NFL concentrations in virologically controlled HIV patients in correlation with clinical variables and neuropsychological testing in men and women compared to matched controls. Methods: 67 patients with chronic HIV-infection on ART for >12months (HIV+) and 21 demographically matched control subjects (HIV-) were included in this study. All participants completed a research lumbar puncture for CSF and a standardized battery of neuropsychological tests. CSF was analyzed for HIV RNA and NFL was analyzed using the QuanterixTM SIMOA Digital Immunoassay. NFL levels were correlated with clinical outcomes including Global Deficit Score (GDS) and average T-scores. An abnormal GDS score (≥0.5) was classified as Neurocognitive Impairment (NCI). Results: There were no significant differences in age, race, or sex between the HIV+ and HIV- groups. In the HIV+ group, plasma viral load was <40 c/mL in 67 (100%), CSF NFL was higher in those with NCI compared to those with a normal GDS (1086pg/mL, 731pg/mL respectively, p<0.01); in the HIV- control group, there were no differences in NFL by cognitive impairment (465pg/mL, 612pg/ mL, p=0.22). Similarly, when looking at average demographically corrected T-scores across the battery of NP tests, higher NFL was associated with lower T-scores only in the HIV group (p=0.03), not in the control group (p=0.88). The Brief Visual Memory Test and Wisconsin Card Sort Test were significantly correlated with higher NFL in the HIV+ group (p<0.001, p<0.01, respectively). In the HIV+ group, this increase in NFL in those with NCI was significant for men only (n=44, p<0.01, Cohen’s d=6.12 for men; n=23, p=0.97, Cohen’s d=0.07 for women). There were no significant associations between NFL and HIV CSF escape (n=7) with CSF HIV > 40c/mL, nadir CD4 (median 206.3 c/mL), time since HIV diagnosis (mean 17.3 years) or time on ART (mean 8.5 years). Conclusion: Even when HIV-infected individuals have been on ART for >12months, there is still a significant association between higher levels of NFL and NCI. This is particularly significant in men, but a larger sample of women is needed to establish a significant effect size to determine whether this association between elevated NFL and NCI can be applied to HIV+ women.

Poster Abstracts

CROI 2019 153