Search for: All records

Abstract HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm the latency reversal properties of in vivo TGF-β blockade, decrease viral reservoirs and stimulate immune responses. Treatment of eight female, SIV-infected macaques on ART with four 2-weeks cycles of galunisertib leads to viral reactivation as indicated by plasma viral load and immunoPET/CT with a⁶⁴Cu-DOTA-F(ab’)₂-p7D3-probe. Post-galunisertib, lymph nodes, gut and PBMC exhibit lower cell-associated (CA-)SIV DNA and lower intact pro-virus (PBMC). Galunisertib does not lead to systemic increase in inflammatory cytokines. High-dimensional cytometry, bulk, and single-cell (sc)RNAseq reveal a galunisertib-driven shift toward an effector phenotype in T and NK cells characterized by a progressive downregulation in TCF1. In summary, we demonstrate that galunisertib, a clinical stage TGF-β inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity. 

This paper presents a real-time locking protocol whose design was motivated by the goal of enabling safe GPU sharing in time-sliced component-based systems. This locking protocol enables a GPU to be shared concurrently across, and utilized within, isolated components with predictable execution times. It relies on a novel resizing technique where GPU work is dimensioned on-the-fly to run on partitions of an NVIDIA GPU. This technique can be applied to any component that internally utilizes global CPU scheduling. The proposed locking protocol enables increased GPU parallelism and reduces GPU capacity loss with analytically provable benefits.