1G) in cohort I. Consistently, in cohort II, Gal-9 treatment induced the levels of tissue-associated HIV DNA (P=0.0019) and RNA (P=0.0.0047) (Figure 1H). These data suggest that the overall impact of Gal-9 treatment on HIV persistence is negative and that Gal-9 expands the levels of tissue-associated HIV reservoirs during ART.Gal-9 treatment does not significantly induce markers of inflammation of T cell activationNext, we examined whether Gal-9 exhibits its adverse effects on HIV persistence by inducing T cell activation/exhaustion or systemic inflammation. We first examined markers of T cell (both CD4+ and CD8+) activation in blood and spleen (collected Figure 1. Gal-9 treatment is tolerable in vivo but induces levels of tissue-associated HIV DNA and RNA in vivo during ART-suppressed HIV infection1A). We did not observe any effect of Gal-9 treatment on the weight of the mice from both cohorts (Figure 2C-D), suggesting that the Gal-9 treatment, at this concentration, was generally tolerable in ART-suppressed HIV-infected humanized BLT mice. Plasma HIV viral loads shown in Figure 1E-F suggest that, in both cohorts, the infection was successful and resulted in high viral loads by the second week post-infection and that ART was able to suppress the virus to below the limit of detection. We have not observed any viral blips in the Gal-9 treated mice to suggest any significant viral reversal effects. We next examined the levels of cell-associated HIV RNA and DNA in tissues. We found that Gal-9 treatment induced the levels of both tissue-associated HIV DNA (P=0.0007) and RNA (P=0.0106) (Figure (A) a schematic overview of the study design. (B) percentage of human CD45+ cells measured in the peripheral blood of BLT mice. (C-D) mice weight over time in cohort I (C) and cohort II (D). (E-F) plasma viral load measured by ddPCR over time in cohort I (E) and cohort II (F). (G-H) Gal-9 treatment-induced levels of tissue-associated HIV DNA and HIV RNA (measured by qPCR) than controls in both cohort I (G) and cohort II (H).99
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