Shock and kill, but don't miss the target

Abstract

Definitive cure of HIV-1 infected patients is limited by the persistence of viral reservoirs under cART, where the interruption of the latter usually precipitates a viral rebound. Main therapeutic approaches used so far, namely the “shock and kill” and the “block and lock” strategies, have been unsuccessful [1]. In concept, the “shock and kill” strategy relies on transcriptional activation of the HIV-1 LTR by multiple compounds including PKC and MAPK agonists, CCR5 antagonist, SMAC mimetics, inducers of PTEFb release, Akt activators, benzotriazole derivatives, epigenetic modifiers such as HDACi, HMTi, and DNMTis, Tat vaccine, as well as immunomodulatory LRAs such as TLR agonists, IL-15 agonist and immune checkpoint inhibitors [2,3].