CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

negatively correlated with rsFC between posterior subgenual ACC and left uncus (p<0.05). Conclusion: We found that depression symptoms were associated with altered rsFC of ACC regions in AHI, consistent with previous neuroimaging literature in depression. Longitudinal research in this cohort will be necessary to determine whether these early alterations in rsFC of ACC are associated with long-term depression symptoms and HIV-related biological factors after antiretroviral therapy.

458 LOWER FRONTAL GREY-MATTER BRAIN VOLUMES AND BASAL-GANGLIA ENLARGMENT IN PERINATAL HIV Beatriz Ruiz-Saez 1 , Manuela Martín-Bejarano 2 , Ana Martinez de Aragon 2 , Pablo Rojo Conejo 2 , Talía Sainz 3 , Alberto Alvarez 3 , José Tomás Ramos 4 , Sara Guillen 5 , Dolores Falcón 6 , Mario Gil-Correa 7 , Pilar Fernández 1 , Santiago Jimenez de Ory 1 , Maria Luisa Navarro 1 , María Isabel González-Tomé 2 , for the NeuroCoRISpe 1 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Hospital La Paz Institute for Health Research, Madrid, Spain, 4 Hospital Universitario Clínico San Carlos, Madrid, Spain, 5 Hospital de Getafe, Madrid, Spain, 6 Hospital Universitario Virgen del Rocio, Sevilla, Spain, 7 Universidad Rey Juan Carlos, Madrid, Spain Background: Brain volume loss has been observed in HIV patients despite initiation on combined antiretroviral treatment (cART), but studies on perinatally HIV-infected patients (PHIV) are scarce. We aim to evaluate the neurologic state and neuroimaging phenotype of stable PHIV youths. Methods: Cross sectional study. 30 PHIV patients and 33 HIV negative peers (HIV-) matched by age, sex and socioeconomic status (SES) participated. Magnetic Resonance Imaging (MRI) and neuropsychological (NP) testing was conducted. The Computational Anatomy Toolbox (CAT12) standard processing pipeline was used for quantification of the MRI T1-W images. Native segmented images were parceled in regions of interest (ROI) and tissue volumes (mm3) were estimated for each ROI and normalized by total intracranial volume for each subject. These normalized data were used to explore differences between groups (ANCOVA tests). NP assessment tested fluid intelligence and Processing Speed (PS) by 7 NP tests (PSZ7). Psychopathological symptoms were also obtained. Differences between groups and effects of HIV-related variables on brain volumes were studied using appropriate statistical tests. Results: 63 participants were included (58.7% females, median age 20 years [IQR 19-23], 65.1% caucasians). No differences regarding level of education, fluid intelligence, PSZ7 or psychopathological symptoms were found between groups. Regarding PHIV: 40% AIDS (13% encephalopathy), median CD4% nadir 11(IQR 5-17). At assessment, 80% had viral load <50 cp/ml (uVL) , median CD4 706 cel/mm3 (IQR 488-916), median time on cART 16.6 years (IQR 13.3-18.5) and median time with uVL 9.8 years (IQR 6.4-12.4). No differences were observed between groups for total grey matter (GM), total white matter, total intracranial volume or cerebrospinal fluid. In relation to GM regional volumes, a decrease was observed in PHIV in left(l) Inferior Frontal Gyrus, right(r) Inferior Frontal Orbital Gyrus, and Median Precentral Gyrus(r) when compared with HIV- (p=0.019, p=0.029, p=0.031). Regarding basal ganglia (BG), larger volumes in caudate(r/l) were associated with lower CD4 nadir (%) (p=0.049, p=0.049) and AIDS (p=0.034, p=0.014). AIDS also showed a negative relation with pallidum(r/l) (p=0.001, p=0.009). Conclusion: Despite good control of HIV infection and no differences in PSZ7 values, PHIV show lower volumes in frontal areas. Moreover, a negative correlation between BG volumes and CD4 Nadir and AIDS suggests that HIV may cause structural compromise to these regions.

Poster Abstracts

459 BENEFICIAL EFFECTS OF CANNABIS ON BLOOD-BRAIN BARRIER AND INFLAMMATION IN HIV Ronald J. Ellis 1 , Jennifer Iudicello 2 , Erin Morgan 1 , Brook Henry 1 , Rachel Schrier 2 , Mariana Cherner 2 , Martin Hoenigl 2 , Scott L. Letendre 2 , for the Translational Methamphetamine Research Center 1 University of California San Diego, La Jolla, CA, USA, 2 University of California San Diego, San Diego, CA, USA Background: HIV infection is associated with increased permeability of the blood-brain barrier (BBB), which may permit increased entry of toxins with consequent CNS injury. Cannabis, which is commonly used among people living with HIV (PLWH); has anti-inflammatory effects; and stabilizes the BBB in animal models. One potential mechanism of increased BBB permeability is upregulation of the urokinase plasminogen activator (uPA), a matrix-degrading proteolytic enzyme, and its receptor, uPAR, disrupting the basal lamina around cerebral capillaries. This study sought to determine the effects of recent cannabis use on cerebrospinal fluid (CSF) concentrations of uPAR, CSF-to-serum albumin ratio (CSAR, an indicator of BBB permeability), and neuroinflammation among PLWH. Methods: Participants were 45 recent (i.e., within the past month) cannabis users with (HIV+) or without HIV (HIV-) who were comparable in age (mean age=39.3) and sex (93.3%male). CSF levels of soluble uPAR, soluble CD14 (sCD14) and CXCL-10 were measured by immunoassay. Albumin was measured in CSF by nephelometry and in serum by a clinical assay. Data were analyzed using standard statistical methods, including regression and t-tests. Results: A statistically significant interaction (p=0.025) was present between HIV and cannabis use frequency (total days over the past month): more frequent use of cannabis was associated with lower concentrations of uPAR in CSF in the HIV+ group (p=0.043) but not in the HIV- group. The CSAR showed similar but non-statistically significant effects. Within the HIV+ group, higher CSF uPAR levels correlated with higher CSAR values (rho=0.47; p<0.001), and more inflammation [higher concentrations of CXCL-10 (p=0.003) and sCD14 (p<0.0001)]. Conclusion: These preliminary findings suggest that cannabis may have a beneficial impact on HIV-associated BBB injury and neuroinflammation. Given the role of the BBB in HIV-associated CNS injury, these results support the potential therapeutic role of cannabis among PLWH, and may have important treatment implications for antiretroviral therapy effectiveness and toxicity.

CROI 2019 168