Individuals living with HIV can be functionally but not permanently cured. The shock and kill method is one of the strategies under investigation to clear the HIV viral latent reservoir. This method aims to activate resting T cells with integrated HIV genome, using latency-reversing agents (LRAs), followed by the killing of these infected cells by CD8 T (and natural killer) cells. More at Is shock (kick)-and-kill HIV cure strategy achievable? More at Is shock (kick)-and-kill HIV cure strategy achievable?
In a recent study, Lu and colleagues investigated whether reactivation of individual latent cells occurs stochastically in response to LRAs or is a deterministic outcome of an underlying cell state. Using Jurkat latency model of HIV-1 (a cell line of Jurkat T cell with a single integration site of the HIV-1 GFP+ genome) and activation of HIV-transcription using TNF, they showed responsiveness (expression of Viral) RNA is inherited and maintained in proliferating cells. However, some of the proliferating cells do become irresponsive, resulting in the maintenance of the viral reservoir. Further, results from mathematical modelling suggest that responsiveness to LRAs is maintained for weeks to months. Thus designing shock- and kill strategies based on multiple rounds of LRA treatment may be more effective than a single-round, single-LRA treatment.
Though this study primarily focused on the shock part of the shock- and kill- strategy, they do provide cues for how this strategy (still in experimental) phase can be improved.
Also read Nixon et al. 2020. Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo. Nature and
McBrien et al. 2020. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells. Nature