CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

469 Predictors of Neurocognitive Decline Among Aviremic Individuals in the CHARTER Cohort Marie-Josée Brouillette 1 ;TracyYuen 2 ; Susan C. Scott 2 ; Lesley K. Fellows 3 ; Robert Heaton 4 ; Scott Letendre 4 ; Ronald J. Ellis 4 ; Nancy Mayo 2 the CHARTER group

1 McGill University Health Centre, Montreal, Canada; 2 McGill University Health Centre, Montreal, Canada; 3 Montreal Neurological Hospital, Montreal, Canada; 4 University of California San Diego, San Diego, CA, US Background: Limited information is available on the predictors of neurocognitive (NC) decline in individuals with good virological control. Identification of modifiable risk factors that predict decline would support the development of targeted interventions aimed at minimizing NC decline in higher-risk individuals. The objective of the study was to identify baseline factors predicting NC decline over the subsequent 3 years in aviremic individuals. Methods: As part of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study, HIV+ individuals were administered 15 neuropsychological tests every 6 months. Group-based trajectory analysis was used to detect patterns of NC change on each test over the course of follow-up. Individuals who deteriorated ≥ 0.5 SD on at least 1 test within the first 36 months of follow-up were considered decliners. Multiple logistic regression was used to identify baseline socio-demographic, clinical, biological and lifestyle factors associated with decline. Results: 191 patients evaluated semi-annually were aviremic at all time points in the first 3 years; 166 had undergone CSF analysis. Viral presence in CSF was rare (10 /649 person- visits). Among the 191 patients, 23 (12%) declined cognitively over 3 years. In the multivariate analysis, the factors at baseline that met our threshold for predicting NC decline are listed in Table 1. Some risk factors identified in prior cross-sectional studies did not predict decline in this sample: older age, non-white ethnicity, low nadir CD4, CPE score, hepatitis C co-infection, diabetes, hypertension, low hemoglobin, low platelets, or a diagnosis of AIDS.

Table 1: Factors predicting NC decline over 36 months in aviremic HIV + people individuals in CHARTER Conclusions: It is encouraging that cognitive decline over 3 years was uncommon in this sample of aviremic HIV+ individuals. The strongest predictor of decline was eGFR, a known independent predictor of atherosclerotic vascular disease. While an extension of this work in a larger sample will be needed to further clarify the contribution of vascular factors to cognitive decline in aviremic individuals, this work suggests that controlling additional cardio-vascular risk factors could be a useful strategy for minimizing cognitive decline. Modifiable risk factors were very common in the entire cohort, with as many as 80% reporting either smoking or a BMI ≥ 25. Smoking cessation and avoidance of obesity would be obvious starting points to maintain brain health. 470 Association Between Plasma Homocysteine Levels and Neuronal Injury in Untreated HIV Erika Ahlgren 1 ; Lars Hagberg 1 ; Lars-Magnus Andersson 1 ; Staffan Nilsson 2 ; Dietmar Fuchs 3 ; Henrik Zetterberg 1 ; Magnus Gisslén 1 1 University of Gothenburg, Gothenburg, Sweden; 2 Chalmers University of Technology, Gothenburg, Sweden; 3 Innsbruck Medical University, Innsbruck, Austria Background: Many HIV-1 infected patients without antiretroviral treatment suffer from neurological symptoms in a varying range of severity. Most patients with, and several without, neurological symptoms have elevated levels of neurofilament light protein (NFL) in cerebrospinal fluid (CSF), a marker of ongoing axonal injury. Hyperhomocysteinemia, related to vitamin B12 and folic acid deficiency, is associated with neurological symptoms. HIV-negative subjects with hyperhomocysteinemia and mild cognitive impairment show a significant reduction of brain atrophy in parts of the brain related to Alzheimer’s disease when treated with vitamin B12. The aim of this study was to investigate the correlation between homocysteine levels in plasma and signs of axonal injury in HIV-1 infected patients. Methods: Homocysteine and B12-vitamin levels were analyzed in plasma with stable isotope dilution liquid chromatography tandemmass spectrometry (LC-MS/MS), and electrochemilluminescence immunoassay, respectively, from 80 neurological asymptomatic HIV-1 infected patients without antiretroviral treatment. NFL was measured, by an enzymatic 2-site quantitative immunoassay (UmanDiagnostics, Umea, Sweden), in CSF, and HIV RNA, neopterin and albumin in blood and CSF. 22 patients provided a second CSF and blood sample, in median 12.5 months, after antiretroviral treatment initiation. Results: We found a significant correlation between the plasma level of homocysteine and CSF level of NFL in untreated patients, (r = 0.52, p <0.0001). 20 patients had hyperhomocysteinemia (>15 m mol/L) and 20 had elevated levels of CSF NFL (age dependent). As expected, there was also a significant inverse correlation between homocysteine and B12 levels (r = -0.41. p <0.001) but no significant correlation between B12 and CSF NFL. CSF neopterin correlated with CSF NFL (r s = 0.30, p = 0.008) but not with serum homocysteine. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1 infected individuals. No significant difference was found in homocysteine levels before and after initiation of antiretroviral treatment. Conclusions: A significant correlation was found between plasma homocysteine and CSF NFL levels in neurologically asymptomatic HIV-1 infected individuals without antiretroviral treatment. These data call for further research into the role of homocysteine or functional vitamin B12 deficiency in CNS injury in HIV-1 infected patients. 471 Plasma MicroRNA Profiling Predicts HIV-Associated Neurocognitive Disorder Background: HIV-associated neurocognitive disorder (HAND) is common, affecting 30-50% of HIV-infected patients despite the availability of effective antiretroviral therapy. The development of HAND is influenced by several factors including altered host and viral gene expression. Host-encoded microRNAs (miRNAs) regulate both host and viral gene expression. Thus, host miRNAs could contribute to the pathogenesis of HAND but also serve as biomarkers of diagnosis and prognosis as well as indicators of underlying disease mechanisms of HAND. Herein, we investigated plasma microRNA profiles among HIV/AIDS patients with and without HAND. Methods: Plasma microRNAs was measured in age and sex-matched HAND (n=22) or nonHAND (n=25) patients (Cohort 1) by array hybridization (Affymetrix 3.0 miRNA genechip). Two software packages (Affymetrix Expression Console and Gene Spring) were used to normalize data and determine differentially expressed miRNAs. The median of each probeset in the HAND or nonHAND was calculated after normalization and differentially expressed miRNAs were identified. A second cohort (Cohort 2) consisting of prospectively recruited age- and sex-matched HAND (n=12) and nonHAND (n=12) patients was used to validate the miRNA profile in Cohort 1. Results: Analyses of comparative expression identified 13 miRNAs in Cohort 1 that were up-regulated with a fold change (FC) of greater than 2 in the HAND group compared to the nonHAND group with one or both computational tools (p<0.05). Analysis of Cohort 2 confirmed up-regulation of 3 miRNAs identified in Cohort 1. In a univariate logistic regression analysis education level, CD4 and nadir CD4 T cell levels and these three miRNAs predicted HAND status based on p -values and odd ratios. Prediction of HAND status by Eugene L. Asahchop 1 ;William G. Branton 1 ; Segun M. Akinwumi 2 ; Noshin Koenig 3 ; Esther Fujiwara 2 ; John Gill 3 ; Christopher Power 1 1 University of Alberta, Edmoton, Canada; 2 University of Alberta, Edmonton, Canada; 3 Southern Alberta Clinic, Calgary, Canada

Poster Abstracts

320

CROI 2015