US researchers have conducted a study that challenges the ‘shock and kill’ approach to treating HIV, suggesting new treatment strategies are needed.
The viral disease is currently considered incurable because of latently infected cells that host the dormant virus after treatment.
The ‘shock and kill’ approach is designed to use latency-reversing agents (LRAs) to shock the infected cells into generating HIV again, while antiretroviral therapy (ART) is maintained to prevent the occurrence of new infections.
This reactivation of the virus allows the ART to directly or indirectly kill the shocked cells.
The team from Buck Institute for Research on Aging conducted a study to investigate the reason behind the ineffectiveness of existing LRAs.
They created a new dual-fluorescence HIV-1 reporter virus called HIVGKO to explore how well different LRAs responded to infection in latent cells. Less than 5% of latently infected cells were reactivated by these agents.
Using sequencing analysis on reactivatable and non-reactivatable HIV infection, the researchers found that the reactivatable virus sites are distinguishable from those that do not respond to LRAs.
Buck Institute for Research on Aging president and CEO Eric Verdin said: “Together, these results indicate that while ‘shock and kill’ might be helpful in reactivating and possibly eliminating a small subset of highly reactivatable latent HIV genomes, other approaches will be necessary to control or eliminate the less readily reactivatable population identified both here and in patients.”
Verdin added that such a cell population must potentially be ‘blocked and locked’ with latency-promoting agents.