Selection of effective LRAs using a newly designed in vitro HIV latency reactivation protocol: toward future application in HIV samples

The “shock and kill” strategy aims to eliminate latent reservoirs by inducing viral transcription through latency-reversing agents (LRAs) thereby exposing infected cells to immune-mediated clearance. We developed and validated a simple, low-cost and highly reproducible in vitro screening protocol to evaluate the efficacy and safety of LRAs, using a two-color flow cytometry assay on ACH2 cells, a well-characterized model of HIV-1 latency.

Using this method, we identified PEP005 and CUDC-907 as the most potent LRAs across multiple experimental settings. Their reactivation capacity was further confirmed through transcriptomic analysis, which revealed a significant upregulation of viral RNA copies following stimulation. In addition, we collaborated with Dompé for using the Exscalate platform, an innovative Computer-Aided Drug Discovery approach, together with the experimental validation, led to the identification of Tandutinib, a tyrosine kinase and mTOR inhibitor, as a novel LRA candidate with appreciable latency-reversing activity in the ACH2 model.