Fig. 8: Targeting sialic acid/Siglec interactions enhances the anti-HIV activity of 10-1074 in a humanized mouse model of HIV infection.

a Study design outlining the generation of 15 female humanized NSG mice engrafted with human memory CD4⁺ T cells, followed by HIV_SUMA infection and weekly treatment with 10-1074 or 10-1074-SiaD (0.75 mg/dose). Monocytes and NK cells were injected weekly. Control mice were treated with PBS only (n = 5 per group). b Peripheral blood human CD4⁺ T cell counts before HIV_SUMA infection, measured by flow cytometry. c Humanized NSG mice were infected intravenously with 1500 TCID₅₀ of HIV_SUMA. Establishment of infection was confirmed by measuring HIV viral load (VL) prior to treatment initiation. d, e Weekly plasma viral load, measured as HIV copies/mL (y-axis) over the experimental duration (x-axis) (d), and presented as AUC (e) to represent cumulative HIV infection over time across the three groups. f, g Mice were weighed weekly, starting before engraftment and continuing until the end of the study. Data are presented as percentage changes from the initial weight (y-axis) over the experimental duration (x-axis) (f). AUC (g) was calculated to represent the cumulative weight change over time. h, i Absolute CD4⁺ T cell counts in peripheral blood (y-axis) was calculated weekly post-engraftment (h) and presented as AUC (i) to represent cumulative CD4⁺ T cell levels over time. Error bars represent the mean ± standard error of the mean. Statistical analyses were performed using the Kruskal-Wallis test, corrected by the two-stage step-up procedure of Benjamini, Krieger, and Yekutieli. j Heatmap representing the protein levels of several human pro-inflammatory markers in plasma across the three treatment groups, before (day 34) and after HIV infection and treatment initiation (day 48). Red indicates higher marker abundance, while blue indicates lower abundance. P-values were computed using two-sided paired t tests. Data in panels (b–j) were generated with n = 15 mice (five mice per each of the three groups).