Wake me up before you go: a strategy to reduce the latent HIV reservoir.

In the quest to eliminate or reduce the HIV reservoir, shock and kill strategies require the combined administration of a latency reversing agent (LRA) to reactivate the latent reservoir and an intervention to boost effector functions to clear this reservoir. Both parts of this strategy are quite inefficient when LRAs are administered to HIV-infected individuals on suppressive ART for several years, possibly due to low levels of induced antigen expression, negative impact of LRAs on clearance mechanisms, and very low number of effective cytotoxic T cells (CTLs). Here we provide rationale for an approach that would require only the administration of an LRA at the time of ART initiation to significantly reduce the HIV reservoir. The advantage of this strategy is an efficient reactivation of the latent HIV reservoir when high numbers of HIV-specific CD8 T cells are present. This strategy may also potentiate more effective CTL responses and the establishment of a longer period of immune surveillance. This “window of opportunity” has been validated , can be tested in preclinical non-human primate (NHP) models and translated rapidly in the clinic.