CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: We have invoked, for the first time, a novel, data driven method for identifying trajectories to cognitive impairment in men with, or at-risk for HIV infection. These results provide new insights into the natural and treated history of HIV/AIDS and suggest that premature cognitive impairment remains a concern, particularly for those individuals infected with HIV who develop AIDS. 494 Brain Structural Correlates of Trajectories to Cognitive Impairment in HIV Disease James T. Becker 1 ; Mikhail Popov 1 ; Samantha A. Molsberry 1 ; Fabrizio Lecci 2 ; Brian Junker 2 ; Sandra Reynolds 3 ; Eric Miller 4 ; Cynthia A. Munro 5 ; Ann Ragin 6 ; Ned Sacktor 5 1 University of Pittsburgh, Pittsburgh, PA, US; 2 Carnegie Mellon University, Pittsburgh, PA, US; 3 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 4 David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, US; 5 Johns Hopkins University School of Medicine, Baltimore, MD, US; 6 Northwestern University, Feinberg School of Medicine, Chicago, IL, US Background: We have described trajectories to mild/severe cognitive impairment among participants in the MultiCenter AIDS Cohort Study (MACS). The goal of this analysis was to determine the relationship between patterns of brain atrophy and membership weights in the individual trajectories among men with brain MRI scans. Methods: A total of 293 (160 HIV-infected; mean age = 55.9 yrs.; mean education: 16.4 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (in SPM8) to segment the brain images into gray matter (GM), white matter and CSF volumes. The analysis used smoothed (8x8x8 mm FWHM) GM images. The trajectory model was created using data from 3,892 MACS participants and had identified three trajectories - a “normal aging” profile with relatively low probability of even mild impairment until well into middle age, a “premature aging” profile with a probability of mild impairment climbing at age 45-50; and, an “unhealthy” profile with a high probability of mild impairment even at a very young age. Each study participant had a membership weight for each of these trajectories. Because these weights are parameter estimates, we used multiple imputation methodology to account for the uncertainty in memberships weights in the correlation analyses. We estimated model parameters with SPM8 for 100 imputations, manually performed the post-hoc contrasts, and pooled the results accounting for between– and within–imputation variability. Results: The results of the analyses (as R 2 ) are shown in Figure 1. The areas colored in Red/Yellow are those whose volume is associated with the membership weight for the “unhealthy” profile; those in Blue/Green are associated with the “premature aging” profile. The unhealthy profile is linked to areas associated with cognitive decline, including the posterior cingulate/precuneus, the hippocampus, and the inferior frontal cortex. Premature aging membership weights are linked to the cingulate gyrus, the insula, and the basal ganglia.

Poster Abstracts

Conclusions: Trajectories to cognitive impairment in HIV disease are the result, in part, of atrophy in brain regions linked to HIV disease (basal ganglia), as well as cortical regions linked with normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy. 495 Cognitive Reserve and Neuropsychological Functioning in Older HIV-Infected People Benedetta Milanini 1 ; Nicoletta Ciccarelli 1 ; Silio Limiti 1 ; Pierfrancesco Grima 2 ; Massimiliano Fabbiani 1 ; Barbara Rossetti 3 ; ElenaVisconti 1 ; EnricaTamburrini 1 ; Roberto Cauda 1 ; Simona Di Giambenedetto 1 1 Institute of Infectious Diseases, Catholic University of Sacred Hearth, Rome, Italy; 2 Division of Infectious Diseases, “S. Caterina Novella” Hospital, Galatina, Italy; 3 Division of Infectious Diseases, University of Siena, Italy Background: Progress in treatments has led to HIV-infected patients getting older. Both age and HIV are risk factors for cognitive decline. We explored the role of cognitive reserve (CR) to the maintenance of neuropsychological integrity in older HIV-infected people. Methods: We performed a multicenter study, consecutively enrolling asymptomatic HIV+ patients ≥ 60 years old during routine outpatients visits. A comprehensive neuropsychological battery (exploring learning, attention, fine motor skills, language and working memory) was administered. All participants also underwent the TIB, an Italian version of the National Adult Reading Test, which is correlated with the Intelligence Quotient (IQ), and the Cognitive Reserve Index (CRI) questionnaire, which includes three sections: education, working activity and leisure time. For each cognitive test, raw scores were transformed into Z-scores; cognitive impairment was defined according to Frascati criteria. Relationships between TIB, CRI and cognitive performance were investigated by logistic or linear regression analyses. Results: Fifty patients [86%males, median age 66 years (range 60-83), 12% HCV co-infected, 4% past IDU, 24%with past AIDS-defining events, 30% affected by diabetes, median CD4 cells count 570/ μ L (IQR 465-747), median nadir CD4 cells count 104/ μ L (IQR 50-239), all on cART (40% on NNRTI and 60% on PI) and with HIV-RNA<50copies/mL] were enrolled. Nineteen patients (38%) showed an Asymptomatic Neurocognitive Impairment (ANI). Median CRI and TIB scores were 114 (IQR 98-134) and 113 (IQR 105-116), respectively; these two measures resulted significantly correlated (r s =0.70; p<0.001). At logistic regression analysis, only CRI (OR 0.95; 95% CI 0.91-0.98; p=0.004) and TIB (OR 0.81; 95% CI 0.71-0.92; p=0.001) were associated with a lower risk of ANI. Higher CRI and TIB were significantly correlated with a better performance (medium Z-score) both globally and at each cognitive domain, except for working memory; for this domain, diabetes was the only variable associated with a worse performance (B -0.39; 95% CI -0.73; -0.50; p=0.025) after adjusting for previous cardiovascular events (B -0.24; 95% CI -0.55; -0.76; p=0.134). Conclusions: Our findings highlight the role of IQ and CR over clinical variables in the maintaining of cognitive integrity in a virologically-suppressed older HIV-infected population. A lifestyle characterized by intellectual and social nature leisure activities may help to cope aging and HIV-related neurodegeneration.

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CROI 2015