Reactivating latent SIV and HIV

To eradicate HIV infection, the virus needs to be flushed out of latently infected cells and then eliminated: this is the rationale behind the so-called ‘shock-and-kill’ approach to cure HIV. To date, methods to shock the virus out of hiding have been suboptimal and inefficient. Two studies now report different ways to achieve robust virus reactivation of SIV in macaques and HIV in humanized mice. Guido Silvestri and colleagues use an interleukin-15 superagonist in conjunction with CD8⁺ lymphocyte depletion to achieve substantial and persistent virus reactivation in all treated animals. Victor Garcia and colleagues use an activator of the noncanonical NF-κB signalling pathway. Although both of these shock approaches will need to be combined with a kill component to achieve clearance of the reactivated virus, these treatments are the most potent latency reversal approaches to date and provide insight into the mechanisms responsible for the maintenance of latency.