CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

margin of change in sCD14 and IFABP in the participants in the low-dose arm, however the reductions were greater for hsCRP and LBP in the high-dose arm. This change was meaningful with large effect size (Cohen’s ranging from 5-19). Conclusion: In this pilot study we found that zinc supplementation is safe and effective at increasing circulating zinc levels. In addition our findings provide novel data that zinc can impact a biological signature in patients with HIV and modulate biomarkers that have been associated with clinical comorbidities.

negatively with fold change in ADCC activity (rho= - 0.52, p=0.026). Last, IFNα-mediated reduction of A2G2S1 glycan trait (p=0.04) correlated positively with change in ADCC activity (rho=0.62, p=0.006), and with IFNα-mediated reduction of integrated HIV DNA levels (rho=0.76, p=0.037). Conclusion: IFNα immunotherapy in HIV-infected individuals on suppressive ART is associated with glycomic alterations, that are known to mediate higher inflammatory responses and higher innate effector functions. Our data suggest that host glycan-lectin interactions may mediate signals that inform and/ or determine host immune responses to HIV persistence during IFN-α treatment.

Poster Abstracts

304 GLYCOMIC DETERMINANTS OF INTERFERON-a MEDIATED REDUCTION OF HIV PERSISTENCE IN VIVO Leila B. Giron 1 , Florent Colomb 1 , Andrew V. Kossenkov 1 , KaramMounzer 2 , Sherry Wang 3 , Jay Kostman 2 , Pablo Tebas 4 , Una O’Doherty 4 , Livio Azzoni 1 , Emmanouil Papasavvas 1 , Luis Montaner 1 , Mohamed Abdel-Mohsen 1 1 Wistar Institute, Philadelphia, PA, USA, 2 Philadelphia FIGHT, Philadelphia, PA, USA, 3 Thermo Fisher Scientific, San Francisco, CA, USA, 4 University of Pennsylvania, Philadelphia, PA, USA Background: Interferon-α (IFNα) therapy was associated with significant suppression of HIV viremia and reduction in levels of HIV DNA during suppressive antiretroviral therapy (ART). Cytokines modulate host glycosylation, and glycosylation plays a critical role in mediating several antibody (mainly immunoglobulin G; IgG) immunological functions, including antibody- dependent cell-mediated cytotoxicity (ADCC), and anti-inflammatory activities. Nevertheless, the impact of IFNα on host glycosylation machinery remains unknown. Methods: We assessed the impact of pegylated IFNα2a (Peg-IFNα2a) immunotherapy on isolated IgG glycomes of 18 HIV-mono-infected individuals on suppressive ART, using capillary electrophoresis. We also examined the plasma levels of 1) the immunomodulatory lectins, galectin-1, -3, -9, E-selectin, P-selectin, and L-selectin; and 2) 16 pro- and anti-inflammatory markers and cytokines, using Luminex. ADCC activity was measured using the Chromium-51 (51Cr) release assay. Last, levels of integrated HIV DNA in CD4+ T cells were examined using qPCR. Wilcoxon signed-rank test and Spearman’s correlations were used for statistical analysis. The Bonferroni method was used to correct for multiple comparisons. Results: Peg-IFNα2a treatment was associated with a significant increase in the proportion of the pro-inflammatory, bisected GlcNAc glycan structures (such as G0FB; Bonferroni-corrected p<0.05). Fold induction of G0FB glycan trait correlated positively with the IFN-α-mediated induction of the pro- inflammatory soluble markers (sCD14 and sCD163; rho>0.56, p<0.016). Peg- IFNα2a also induced the plasma levels of the inflammatory mediators galectin-9 (p=0.0001), L-Selectin (p=0.027), and E-Selectin (p<0.008). IFNα2a-mediated reduction of the anti-ADCC total fucosylated glycans (p<0.05) correlated

305 SUSCEPTIBILITY TO BNABs IS CONCORDANT IN PRE-ART PLASMA AND ON-ART PBMCs: ACTG NWC413 Jacqueline Reeves 1 , Yu Zheng 2 , Maxine Olefsky 3 , Yolanda Lie 1 , Leah Burke 4 , Babafemi Taiwo 5 , Christos Petropoulos 1 , Pablo Tebas 6 , Marina Caskey 7 , Katharine J. Bar 6 1 Monogram BioSciences, San Francisco, CA, USA, 2 Harvard University, Cambridge, MA, USA, 3 Harvard University, Boston, MA, USA, 4 Yale University, New Haven, CT, USA, 5 Northwestern University, Chicago, IL, USA, 6 University of Pennsylvania, Philadelphia, PA, USA, 7 The Rockefeller University, New York, NY, USA Background: Pre-existing resistance is a barrier to the efficacy of broadly neutralizing antibodies (bnAbs) for treatment and cure of HIV infection. Here, we determine the range of baseline susceptibilities to bnAbs in clinical development and assess the PhenoSense HIV nAb Assay’s predictive capacity in plasma virus and proviral DNA samples. Methods: HIV envelopes derived from pre-ART plasma and PBMCs from 1 and 3 years of ART from each of 65 chronically HIV-infected participants of the ART naïve trial A5257 were tested for neutralization susceptibility to seven bnAbs (VRC01, VRC07.523LS, 3BNC117, N6, 10-1074, CAP256-VRC26.25, 10E8) using the PhenoSense nAb assay, which generates pseudovirions from plasma vRNA or PBMC proviral DNA-derived HIV envelopes. PBMCs from 9 participants at entry to A5340, which evaluated VRC01 during ART interruption, were also tested. Rank-based Spearman Correlation and Fisher’s exact tests were used for statistical analyses. Results: Participants’ median CD4 count was 350 cells/mm3 and 40% had a baseline VL >100,000 copies/ml. IC50s varied more than 3 logs for each bnAb, but pre-ART plasma, year 1 and 3 PBMC values were highly correlated (Spearman r= 0.62-0.95, P<0.001 for all), with modestly lower IC50s in PBMC samples. Correlations for titers against VRC01 in the 3 samples are shown in Figure 1. Susceptibilities within the CD4 binding site bnAbs were correlated (r=0.71-0.86, P<0.001 for pre-ART plasma). No significant relationships were found between bnAb classes, except a modest correlation between CD4bs bnAbs and 10-1074 (r= 0.29-0.4, P=0.002-0.023). Among the A5340 samples, VRC01 IC50s from entry PBMCs correlated with published pre-ART plasma IC50s

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