CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

385 EXHAUSTED T CELLS AND INFLAMMATORY MONOCYTES ARE LINKED TO BRAIN ATROPHY IN HIV Brooks I. Mitchell 1 , Glen Chew 1 , Kalpana J. Kallianpur 1 , Mary Margaret Byron 1 , Robert Paul 2 , Beau K. Nakamoto 1 , Dominic Chow 1 , Scott A. Souza 1 , Cecilia Shikuma 1 , Lishomwa C. Ndhlovu 1 1 Univ of Hawaii, Honolulu, HI, USA, 2 Univ of Missouri–St. Louis, St. Louis, MO, USA Background: We have previously reported that T-cell exhaustion associated with neurocognitive impairment among HIV-infected adults on stable antiretroviral therapy (ART). Here, we investigated the relationship between immune populations and regional brain volumes. Methods: We utilized flow-cytometry to assess markers of CD8 T-cell activation (CD38+HLA-DR+), senescence (CD57+CD28-), and exhaustion (TIM-3, PD-1 and TIGIT) in peripheral blood mononuclear cells in HIV-infected individuals on stable ART with available regional brain volume data measured by T1-weighted magnetic resonance imaging at 3T as well as monocyte counts for classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical/inflammatory (CD14+/lowCD16++) subsets. Multivariable linear regression was utilized to assess the relationships between the immunophenotypes and regional brain volumes while controlling for intracranial volume and age. Pearson correlations were used in the analysis. Results: Thirty-three HIV+ participants were mostly male (84%) with a median age 52 years, and median current CD4 T-cell count of 479 cells/mm3. Detectable viral load (>50 copies/ml) was noted in 12% of the participants. Higher PD-1+ CD8 T-cell frequencies (%) were associated with lower volumes in the putamen (β= -0.522, p=0.005), nucleus accumbens (β= -0.426, p=0.023), cerebellar cortex (β= -0.389, p=0.042), and subcortical gray matter (β= -0.368, p=0.037) brain regions. Higher % of PD-1+TIM-3+ CD8 T-cells were associated with lower volumes in the putamen (β= -0.533, p=0.003) and nucleus accumbens (β= -0.371, p=0.046), while higher % of PD-1+TIGIT+ CD8 T-cells were only associated with lower volumes in the putamen (β= -0.488,p=0.008). Higher % of PD-1+, PD-1+TIM-3+ and PD-1+TIGIT+ CD8 T-cells were associated with higher counts of inflammatory monocytes (all p<0.05). Even with the exclusion of individuals with detectable viremia, all findings remained significant. No associations were observed for regional brain volumes with % of TIM-3+, TIGIT+, or TIM+TIGIT+ CD8 T-cells or with any of these markers on CD4 T-cells. Conclusion: T-cell exhaustion was associated with lower brain volumes and increases in inflammatory monocytes, suggesting monocyte-T-cell exhaustion may be interrelated processes involved in brain atrophy during ART-treated HIV. Immunotherapy targeting PD-1 in combination with other negative checkpoint receptors may be considered as treatment modalities for HAND and associated structural brain atrophy.

Poster and Themed Discussion Abstracts

386 CSF AND SERUM BIOMARKERS OF NEURONAL INJURY AND AGING IN HIV-INFECTED PARTICIPANTS Sergio M. de Almeida 1 , Clea E. Ribeiro 1 , Indianara Rotta 1 , Mauro Piovesan 1 , Sonia M. Raboni 1 , Scott Letendre 2 , Bin Tang 2 , Florin Vaida 2 , Ronald J. Ellis 2 1 Univ Fed do Paraná, Curitiba, Brazil, 2 Univ of California San Diego, San Diego, CA, USA

Background: The profile of neural injury biomarkers is not well defined in HIV infection, the majority of the studies are on HIV subtype B (HIV1-B). In vitro, HIV1-B Tat protein, inhibits neprilysin, an important amyloid β (Aβ)-degrading enzyme, causing Aβ accumulation. Effects of HIV subtype C (HIV1-C) have not been yet characterized. This study aimed to compare Aβ and related biomarkers between HIV1B (n=27) and C (n=26). Additional comparisons were made to healthy HIV negative (n=18) and Alzheimer disease (AD) patients (n=24). Methods: Immunoassays were used to measure soluble amyloid precursor protein α and β (sAPPα, sAPPβ); Aβ38,40,42 and total; tau phosphorylated at threonine 181(P-tau181); Total tau (T-tau) and neurofilament light(NFL). Comparisons between HIV(+) and HIV(-) were adjusted by linear regression for gender and age. HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. Results: CSF Aβ42 was lower in HIV1-C than B(p= 0.03); the subtypes did not differ in serum biomarkers. Compared to AD, all HIV(+) together (n=68) had lower CSF levels of T-tau, P-tau181,NFL (p <0.001) and sAPPα(p= 0.02); All HIV(+) together had higher CSF levels of Aβ42 (p<0.001) and higher CSF indexes: [Aß42/ (240 + 1.18 T-tau)], P-tau181/AB42, T-tau/Aβ42, P-tau181/T-tau, sAPPα/β (all p<0.01) than AD. In serum HIV(+)<=”” div=””> Conclusion: There was impact of HIV infection on amyloidal metabolism, with difference between subtypes B and C and difference with AD. The finding that Aß42 levels were lower in HIV1C than HIV1B, suggests that there may be greater deposition of Aß42 in HIV1-C than B.

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