CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

408 CD4/CD8 Ratio Decline and Risk of Neurocognitive Deterioration Matteo Vassallo 1 ; Roxane Fabre 2 ; Jacques Durant 3 ; Christine Lebrun-Frenay 2 ; Brigitte Dunais 2 ; Muriel Laffon 2 ; Francine DeSalvador 2 ; Jacqueline Cottalorda 3 ; MichelTicchioni 2 ; Pierre Dellamonica 3 ; Christian Pradier 2 1 Cntr Hospier de Cannes, Cannes, France; 2 Nice Univ Hosp, Nice, France; 3 CHU de Nice, Nice, France Background: Persistent immune activation is among suspected causes of HIV-associated neurocognitive disorders (HAND) in the cART era. The CD4/CD8 ratio has been recently identified as a marker of immune activation and HAND. Our aimwas to investigate a potential impact of CD4/CD8 ratio decline over time on neurocognitive deterioration Methods: Randomly selected HIV-infected patients were included in the Neuradapt study and followed for neuropsychological (NP) testing during a follow-up period of almost 2 years. Tests were adjusted for age, gender and education. Patients were divided into 5 groups: Normal tests (NT), neuropsychological deficit (ND, 1 impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND) and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Results: 256 patients underwent NP tests and 94 completed follow-up. The two groups were comparable. Mean duration of follow-up was 22.4 months At inclusion, 75 patients were male (80%), mean age was 46.3 years (SD=10.8), mean time since HIV infection was 12.1 years, mean CD4 cell count 552.1 cc/mm 3 (SD=273.7), mean nadir of CD4 cells was 262.3 cc/mm 3 (SD=183.1), mean CD4/CD8 ratio was 0.73, 69 subjects (73%) had HIV-RNA below 200 copies/ml and 23 (25%) were HCV co-infected. Upon neuropsychological retesting, 6 patients showed clinical improvement, 30 had worsened and 58 were stable, resulting in 42 patients presenting with HAND (45%). The majority of HAND cases consisted of ANI (26%) and MND (16%). Patients who worsened their NP performances had lower CNS penetration effectiveness (CPE 2010) score at inclusion (7.13 vs 8.00, p =0.003) and higher frequency of CD4/CD8 decrease (60% vs 31%, p =0.008) than those who were stable or improved. Multivariate analysis confirmed that the CPE score at inclusion (OR 0.59, [CI 0.37-0.86], p=0.015) and the slope of the CD4/CD8 ratio over time (OR 3.7 [CI 1.45-9.87], p= 0.007) were independent risk factors for cognitive decline. Conclusions: A decrease of the CD4/CD8 ratio in a longitudinal follow-up of randomly selected HIV-infected patients was independently associated with cognitive decline, suggesting an inflammatory pathway for brain injury. Monitoring the trend in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration. 409 Novel CSF Biomarker Associations With HIV-Associated Neurocognitive Disorder (HAND) Asha R. Kallianpur 1 ; Haley Gittleman 2 ; Scott R. Letendre 3 ; Ron Ellis 3 ; Jill Barnholtz-Sloan 4 ;William Bush 4 ; Robert Heaton 5 ; David Samuels 6 ;Todd Hulgan 7 ; for the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study Group 1 Cleveland Clinic/Lerner Rsr Inst, Cleveland, OH, USA; 2 Case Western Reserve Univ, Cleveland, OH, USA; 3 Univ of California San Diego, San Diego, CA, USA; 4 Case Western Reserve Univ Sch of Med, Cleveland, OH, USA; 5 Univ of California San Diego, La Jolla, CA, USA; 6 Vanderbilt Univ Sch of Med, Nashville, TN, USA; 7 Vanderbilt Univ, Nashville, TN, USA Background: Dysregulated iron transport may promote glial-cell activation and angiogenesis, which are implicated in blood-brain-barrier compromise and some neurodegenerative disorders. We hypothesized that CSF ceruloplasmin (CP), a ferroxidase involved in iron transport, haptoglobin (HP), an iron-binding protein and ligand for the macrophage-monocyte scavenger receptor CD163, and vascular endothelial growth factor (VEGF) are associated with HAND. Methods: CP, HP, and VEGF were quantified by bead suspension array immunoassay in CSF from 405 participants enrolled in the CHARTER cohort who underwent comprehensive neuropsychiatric and neuromedical evaluations. CSF biomarker associations with HAND, defined by a global deficit score (GDS)≥0.5 (GDS impairment) or by Frascati criteria, and with GDS as a continuous measure (cGDS), were evaluated for tertile (T)3 vs. T1, due to non-normality of biomarker distributions, adjusting for antiretroviral therapy, nadir CD4, genetic ancestry, and comorbidity status (contributing vs. incidental to HAND). Analyses stratified by comorbidity and excluding subjects with multiple biomarker values ˃2 SD above the mean were also performed. Results: Higher CSF VEGF was associated with GDS impairment and cGDS in univariate analyses [odds ratio (OR) 2.17 and beta =0.12, respectively; both p<0.05] and remained associated with GDS impairment after adjustment (OR 2.00, p<0.05). GDS impairment was associated with higher CSF CP in adjusted analyses (OR 1.77, p<0.05) and with higher CP and HP in 252 persons with only minimal comorbidities (ORs 2.37 and 2.13, respectively; both p<0.05). In the subset with minimal comorbidities, higher CP and HP levels were also associated with HAND by Frascati criteria (ORs 2.44 and 2.08, respectively, both p<0.05), and increased CP was associated with higher cGDS values (more impairment, p<0.01). Finally, CP and HP were associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p<0.01) and HAND by Frascati criteria (both p<0.01) in persons with undetectable plasma viral load and minimal comorbidities. Weak correlations of CP, HP, and VEGF with concurrently measured IL-6, IL-8, CXCL10, and TNF- alpha were observed. Conclusions: CSF HP and CP are associated with HAND in HIV-infected persons, especially those with minimal comorbidities; VEGF levels are also linked to HAND. Future studies might explore interventions aimed at disordered iron transport and angiogenesis for preventing or treating HAND. 410 (1  3)-ß-D-Glucan Levels CorrelateWith Neurocognitive Functioning in HIV Infection Martin Hoenigl 1 ; Michelli Faria de Oliveira 1 ; Josué Pérez-Santiago 1 ; Malcolm Finkelman 2 ;Yonglong Zhang 2 ; Sheldon R. Morris 1 ; Ron Ellis 1 ; Sara Gianella 1 1 Univ of California San Diego, San Diego, CA, USA; 2 Rsr Lab, Associates of Cape Cod, Inc, Falmouth, MA, USA Background: Microbial translocation from the gastrointestinal tract is associated with persistent inflammation, and might play a role in the pathogenesis of neurocognitive dysfunction during HIV-infection, even in people treated early after seroconversion. (1  3)-β-D-Glucan (BDG) is a polysaccharide component of most fungal species cell walls including Candida spp. In the absence of an active fungal infection, increased blood BDG levels may be an indicator of gut mucosal barrier disruption and microbial translocation. The objective of this study was to evaluate whether higher blood BDG levels correlate with worse neurocognitive functioning (evaluated by global deficit score [GDS]) in a cohort of HIV+ adults on suppressive antiretroviral therapy (ART). Methods: We measured levels of BDG in paired plasma and CSF samples, and compared levels with GDS, soluble (s)CD14 and Interleukin-8 (IL-8) in a cohort of 19 adults with acute/ early HIV diagnosis, early treatment and suppressed levels of HIV RNA in blood plasma throughout treatment. Study samples were collected prospectively between December 2013 and June 2014 at the University of California, San Diego. 19 plasma and 16 CSF samples were stored at -80°C on the day of collection. BDG testing of plasma and CSF supernatant samples was performed in June 2015 at Associates of Cape Cod, Inc., research laboratories using the Fungitell assay. Results: Median GDS was 0.39 (range 0 - 2.67; >0.5 is considered at least mild cognitive impairment). Median plasma BDG level was 66 pg/mL (range: 20-101 pg/mL), median CSF BDG level was 5 pg/mL (range: 0-53 pg/mL). Higher levels of plasma BDG were associated with more severe cognitive impairment as measured by the GDS (Spearman r=0.47; p=0.04, Figure A). Correlation of other markers with GDS scores were as follows: IL-8 (r=0.55; p=0.014), sCD14 (r=0.4, n.s.), nadir CD4 count (r=0.01, n.s.). We found no significant correlation between plasma BDG and IL-8 (r=0.12, n.s.) and plasma BDG and plasma sCD14 (r=0.38, n.s.). Two CSF samples presented elevated BDG levels (45 and 53 pg/mL; Figure B), while all other samples had BDG levels < 10 pg/mL. Interestingly, these two samples originated for the two subjects with the highest GDS scores of the cohort. Conclusions: BDG may be an indicator of gut mucosal barrier disruption and a promising independent biomarker associated with neurocognitive functioning in virologically suppressed HIV infected individuals with high CD4 counts diagnosed and treated

Poster Abstracts

155

CROI 2016