DEVELOPMENT OF SPECIFIC LRAs MOLECULES TO PURGE THE LATENT PROVIRAL POOL OF HIV IN PATIENTS
Although combined antiretroviral therapy (cART) successfully decreases plasma viremia to undetectable levels, the complete eradication of human immunodeficiency virus type 1 (HIV-1) remains impractical because of the existence of a viral reservoir. The Shock & Kill strategy is based on the use of LRAs (latency reversing agents) to re-activate reservoir quiescent cells in order to kill them. Various cytokines, protein kinase C activators/agonists, and histone deacetylase inhibitors (HDACi) have been used as LRAs, but their unacceptable side effects and/or low efficiencies limit their clinical use.
In this project, using molecular modeling, the team has screened and selected new molecules acting as LRAs that do not target a cellular protein but a viral protein. The series was evaluated in vitro, in cellulo and ex vivo using primary quiescent cells purified from HIV-1 patients on ART.
AVAILABLE TECHNOLOGY | HIV – Shock & Kill Strategy – LRAs