The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder

Despite potent suppression of HIV-1 viral replication in the central nervous system (CNS) by antiretroviral therapy (ART), between 15% and 60% of HIV-1-infected patients receiving ART exhibit neuroinflammation and symptoms of HIV-1-associated neurocognitive disorder (HAND) - a significant unmet challenge. We propose that the emergence of HIV-1 from latency in microglia underlies both neuroinflammation in the CNS and the progression of HAND. Recent molecular studies of cellular silencing mechanisms of HIV -1 in microglia show that HIV-1 latency can be reversed both by proinflammatory cytokines and by signals from damaged neurons, potentially creating intermittent cycles of HIV-1 reactivation and silencing in the brain. We posit that anti-inflammatory agents that also block HIV-1 reactivation, such as nu-clear receptor agonists, might provide new putative therapeutic avenues for the treatment of HAND.

Automated summary

Despite the suppression of HIV-1 viral replication in the central nervous system by antiretroviral therapy, a significant percentage of HIV-1-infected patients still experience neuroinflammation and symptoms of HIV-1-associated neurocognitive disorder. Recent studies suggest that HIV-1 latency in microglia plays a role in both neuroinflammation and the progression of neurocognitive disorders. Therefore, anti-inflammatory drugs that can also inhibit HIV-1 reactivation may offer potential therapeutic options for treating these disorders.