CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

429 BRAIN 18F-FDG PET OF SIV-INFECTED MACAQUES AFTER TREATMENT INTERRUPTION OR INITIATION William T. Schreiber-Stainthorp 1 , Sharat Srinivasula 2 , Sanhita Sinharay 1 , Swati Shah 1 , Jing Wang 2 , Lori E. Dodd 3 , H. Clifford Lane 3 , Michele Di Mascio 3 , Dima A. Hammoud 1 1 NIH, Bethesda, MD, USA, 2 Leidos Biomedical Research, Inc, Frederick, MD, USA, 3 NIAID, Bethesda, MD, USA Background: Subtle neurocognitive dysfunction has become more prevalent in the post-antiretroviral (ART) era suggesting continuing neurological damage despite treatment. On the other hand, HIV+ patients often fail to adhere to their treatment due to financial, social, and psychological factors. Our study investigates the effects of treatment initiation and interruption on brain inflammation/immune activation using 18F-FDG (FDG) metabolism in SIV-infected macaques, in correlation with clinical and laboratory markers of disease. Methods: Seven rhesus macaques were infected with SIV and underwent ART- interruption (n=5) and/or initiation (n=5). FDG-PET imaging was performed at baseline and at multiple time points up to 9 months after treatment modification. Mean and maximum Standardized Uptake Values (SUV) for the whole-brain were calculated. Plasma/CSF viral load (VL) and cytokine levels were measured. We evaluated changes in SUV from baseline to one month using a paired t-test. Mixed-effect linear regression models evaluated changes over multiple time-points and the association of SUV with disease markers. Results: Treatment interruption was associated with increased whole-brain SUVmean and max after 1 month (p=0.038; p=0.041) (Fig.1). The change was most pronounced during this early period however time was not statistically significant when evaluated in mixed effect linear regression models over the rest of the follow-up period. Decreased CD4+ and CD8+ cell counts and increased CSF VL were associated with increased SUVmean and max. Similarly increased CSF IL-15 was associated with increased SUVmean. The pattern within the treatment initiation group was far more variable and statistically significant associations were not observed (Fig.1), despite decreased plasma/CSF VL, increased CD4+ and CD8+ counts and decreased plasma/CSF cytokines. Conclusion: In this study, ART interruption was associated with increased brain metabolism, which may reflect neuroinflammation in the setting of viral rebound. These effects were observed within one month of interruption. Although we cannot document permanent neurologic damage in association with increased glucose metabolism, this raises concerns about the potential damage of even brief periods of non-adherence to ART. Treatment initiation, however, did not result in significant changes in brain metabolism. This could be due to the long time needed for neuroinflammation to abate under the effects of viral control, beyond our follow-up period.

430 INTACT STRUCTURAL AND FUNCTIONAL BRAIN IMAGING IN ACUTE HIV Vishal Samboju 1 , Carissa Philippi 2 , Phillip Chan 3 , Yann Cobigo 1 , James L. Fletcher 3 , Merlin L. Robb 4 , Joanna Hellmuth 1 , Khunthalee Benjapornpong 3 , Netsiri Dumrongpisutikul 5 , Mantana Pothisri 5 , Robert Paul 2 , Jintanat Ananworanich 4 , Serena S. Spudich 6 , Victor Valcour 1 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Missouri St Louis, St Louis, MO, USA, 3 SEARCH, Bangkok, Thailand, 4 US Military HIV Research Program, Silver Spring, MD, USA, 5 Chulalongkorn University, Bangkok, Thailand, 6 Yale University, New Haven, CT, USA Background: HIV is identified in cerebrospinal fluid within 8 days of estimated viral exposure. Neurological findings and impaired neuropsychological testing performance are documented in a subset of individuals with acute HIV infection (AHI). The purpose of this study was to determine whether microstructural white matter and resting-state functional connectivity (rsFC) are disrupted during AHI. Methods: We examined 49 AHI (100%male; mean age=30±SD 9.9) and 23 HIV-uninfected (HIV-CO) Thai participants (78%male; age=30±5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four neuropsychological tests (summarized as NPZ4). MRI for the AHI group was performed prior to antiretroviral treatment (ART) in 26 participants and 2 (±1.1) days after ART in 23 participants. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the default mode (DMN), fronto-parietal, and salience and 6 subcortical networks. rsFC and DTI analyses were corrected for family-wise error, with voxelwise comparisons completed using t-tests. Group-specific voxelwise regressions were conducted to examine relationships between imaging indices, clinical variables, and treatment status. Results: The AHI group had a mean (SD) CD4 count of 421 (±234) cells/uL, 6.07(±1.1) log 10 copies HIV RNA and estimated duration of infection of 20 (±5.5) days. There were no differences between AHI and HIV-CO groups for DTI metrics. Within the AHI group, voxelwise analyses revealed associations between brief exposure to ART and higher FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and superior longitudinal fasciculus (p <0.05). Diffusion indices were unrelated to clinical variables or NPZ-4. The AHI group had reduced rsFC between left parahippocampal cortex (PHC) of the DMN and left middle frontal gyrus compared to HIV-CO (p <0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4 count correlated to increased rsFC in the right lateral parietal and PHC seeds in the DMN. NPZ-4 was correlated positively with rsFC in the bilateral caudate seed (p <0.002). Conclusion: Study findings reveal limited disruption to structural and functional brain integrity in the earliest stages of HIV. Longitudinal studies are needed to determine if treatment with ART during AHI is sufficient to prevent the evolution of progressive brain dysfunction in chronically infected individuals. 431 HIV INFECTION AND AGE HAVE INDEPENDENT EFFECTS ON BRAIN GRAY MATTER VOLUME Erin O’Connor 1 , Thomas Zeffiro 1 , Melissa F. Murray 2 , Donna Martineck 2 , James T. Becker 2 1 University of Maryland, Baltimore, MD, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: Although many studies have documented cortical and subcortical white and gray matter volume (GMv) changes following HIV infection (1,2), GMv is also known to decline with age and illicit drug use. As the HIV infected population is steadily aging, the effects of age and past drug use may confound attempts to identify specific effects of serostatus on regional GMv. The effects of age and drug abuse may also complicate the use of brain structural measures more generally in the diagnosis and treatment assessment of HIV-Associated Neurocognitive Disorders. Here we examined the effects of serostatus, age and past drug use on regional GMv. Methods: Participants were 113 seropositive and 88 seronegative men, ages 23-73, with 118 reporting past illicit drug use. Seropositive participants were all treated with anti-retroviral therapies. Regional GMv was estimated using tissue segmentation of 1mm 3 T1-weighted 3-D anatomical brain images. Mixed effects linear regression models were used to explore effects of serostatus, race, age, field strength, intracranial volume and drug use on regional GMv using both a priori regions and Voxel-Based Morphometry. Results: Seropositive participants had bilateral decreases in the volume of the caudate nucleus and putamen, bilaterally (p<0.05 FWE-corrected).

Poster Abstracts

CROI 2018 152