CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

387 CSF S100B AND CX3CR1 MONOCYTES IN ACUTE HIV INFECTION PREDICT PUTAMEN ATROPHY Lishomwa C. Ndhlovu 1 , Kalpana J. Kallianpur 1 , Eugene Kroon 2 , Thep Chalermchai 3 , Khunthalee Benjapornpong 4 , Shelly J. Krebs 5 , Serena Spudich 6 , Jintanat Ananworanich 5 , Victor Valcour 7 , for the RV254/SEARCH010 Study Group 1 Univ of Hawaii, Honolulu, HI, USA, 2 SEARCH, The Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 3 SEARCH, Bangkok, Thailand, 4 Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 5 US Military HIV Rsr Prog, Silver Spring, MD, USA, 6 Yale Univ, New Haven, CT, USA, 7 Univ of California San Francisco, San Francisco, CA, USA Background: We previously reported decreases in brain regional gray matter (GM) volumes over 24 months in individuals who initiated combination antiretroviral therapy (cART) during acute HIV infection (AHI). Here we examined relationships of caudate, putamen, pallidum and total subcortical GM volumetric reductions to peripheral immune activation/inflammation (sCD163, sCD14, IL-6, TNF-α, MCP-1) and neuronal (S100B and neurofilament light protein) markers and to monocyte phenotypes implicated in HIV neuropathogenesis. Methods: We prospectively enrolled individuals with AHI (Fiebig stages I-IV) who underwent brain magnetic resonance imaging (MRI) at 1.5T and then immediately initiated cART. MRI was repeated at 24 months. Biomarkers in cerebrospinal fluid (CSF) were assayed by ELISA or Luminex. Peripheral blood mononuclear cells were assayed by flow cytometry to measure monocyte frequencies based on CD14, CD16, CCR5, CCR2 and CX3CR1 expression. Nonparametric statistics were used. Results: Biomarkers and monocyte frequency data at baseline prior to cART and at 24 months were obtained for 15 participants [14 male; baseline median (range) age=28.0 (19-45) years; exposure time=15 (8-28) days; CD4 count=339 (132-740) cells/mm3; plasma HIV RNA=5.53 (2.78-7.56) log10 copies/mL]. Regional volumes at both timepoints were available for 13 individuals. S100B increased from 966 (540-1493) pg/mL at baseline to 1024 (649-1590) pg/mL at 24 months post-ART initiation (p=0.009). At baseline, higher S100B correlated with higher frequencies (%) of non-classical (patrolling/inflammatory) monocytes (ρ=0.56, p=0.029), and on a per cell basis for non-classical monocytes expressing CX3CR1, a receptor that facilitates monocyte migration and survival (ρ=0.64, p=0.010). % decrease in putamen volume from baseline to 24 months post-cART correlated positively with baseline S100B (ρ=0.58, p=0.002) and with baseline % CX3CR1+monocytes (ρ=0.76, p=0.004). Conclusion: S100B, serves as a marker of brain damage and AHI participants exhibited an increase in CSF S100B over 24 months despite immediate initiation of cART. CSF S100B in AHI may predict atrophy of the putamen, a region which has been suggested to be preferentially susceptible to early HIV-related damage (Wright et al, 2016). CX3CR1 monocytes may penetrate the brain and be involved in neuronal-microglial interactions that contribute to brain volumetric changes ultimately reflected by elevated CSF S100B.

Poster and Themed Discussion Abstracts

388 TELOMERE LENGTH: NEUROCOGNITIVE BIOMARKER IN HIV-1–INFECTED SUBJECTS Marília L. Araújo 1 , Maria Rita. P Gascón 2 , Raquel Paiva 3 , Bárbara Santana 3 , Rodrigo Calado 3 , Wellington Duarte 1 , Luiz A. Fonseca 1 , Augusto César P. Oliveira 2 , Jorge Casseb 1 1 Univ de São Paulo, São Paulo, Brazil, 2 Inst de Infectologia Emílio Ribas, São Paulo, Brazil, 3 Univ de São Paulo Ribeirão Preto, Ribeirão Preto, Brazil Background: HIV associated neurocognitive disorders (HAND) remain a serious problem today because of the high prevalence of their milder forms. HIV-positive individuals have substantially shorter telomeres in peripheral blood mononuclear cells and in CD8 + T cells compared to HIV negative individuals. Given the above, the objective of this study was to evaluate the association of telomere length of leukocytes (LTL) in HIV-infected individuals with cognitive disabilities, since it remains a very controversial subject. Methods: A total of 73 patients of both sexes, infected with HIV-1 and aged 20 to 60 years, participated in this study: Nineteen HIV-1-positive patients without cognitive impairment and 54 HIV patients (+) with neurocognitive disorders, namely: 29 with asymptomatic neurocognitive disorder (ANI), 15 with mild to moderate neurocognitive disorder (MND) and 10 with HIV-associated dementia (HAD); 118 HIV-negative individuals made up the control group. All participants underwent a series of previously validated neuropsychological tests. HIV-1 viral load was determined in cerebrospinal fluid cells (CSF) and in PBMC. We used DNA from peripheral leukocytes to calculate the length of telomeres by real time PCR. Statistical analysis: We used Mann Whitney test for the analysis of nonparametric variables, and the Spearman and Pearson’s r tests for analysis of correlation where appropriate. Results: Telomere length was not associated with sex (p=0.85) and decreased with age (p=0.0001), irrespective of HIV status. HIV-1-infected individuals with milder forms of neurocognitive impairment had a significantly shorter telomere length as compared with HIV-positive patients without neurocognitive impairment (p=0.038). There was no correlation between plasma viral load and the size of telomere (p=0.66). Conclusion: Our results suggest that telomere length can be a cell senescence marker in subjects with HAND.

CROI 2017 156