Shocking HIV-1 with immunomodulatory latency reversing agents

The shock-and-kill strategy is one of the most explored HIV-1 cure approaches to eliminate latent virus. This strategy is based on HIV-1 reactivation using latency reversing agents (LRAs) to reactivate latent proviruses (the shock phase) and to induce subsequent elimination of the reactivated cells by immune responses or virusinduced cytopathic effects (the kill phase). Studies using immunomodulatory LRAs such as blockers of immune checkpoint molecules, toll-like receptor agonists, cytokines and CD8(+) T cell depleting antibodies showed promising potential as LRAs inducing directly or indirectly cellular pathways known to control HIV transcription. However, the precise molecular mechanisms by which these immunomodulatory LRAs reverse latency remain incompletely understood. Together with the heterogenous nature of HIV-1 latency, this lack of understanding complicates efforts to develop more efficient and safer cure strategies. Hence, deciphering those mechanisms is pivotal in designing approaches to eliminate latent HIV infection.

Automated summary

The shock-and-kill strategy relies on latency reversing agents (LRAs) to reactivate HIV-1 and induce immune responses or cytopathic effects for elimination of latent virus. LRAs, particularly immunomodulatory ones, show potential for controlling HIV transcription pathways, but the precise mechanisms are not fully understood, complicating efforts to develop more efficient and safer cure strategies. Deciphering these mechanisms is crucial in designing approaches to eliminate latent HIV infection.