Unveiling the Role of Microglia in HIV-Associated Neurodegeneration: Current Insights and Future Directions
Author(s): Pratiksha S. Pansambal and Swarali N. Kurle
HIV has affected approximately 84.2 million individuals to date. Antiretroviral treatment (ART) has resulted in reduced disease severity and improved quality of life for people living with HIV. Despite the effectiveness of ART, HIV-associated neurocognitive disorders (HAND) continue to present significant challenges in managing individuals with HIV. As the primary immune cells of the central nervous system (CNS), microglia play an active role in maintaining homeostasis and responding to neuroinflammatory stimuli. The virus can infiltrate the brain, establishing a persistent reservoir that leads to chronic immune activation and inflammation. Consequently, microglia undergo phenotypic and functional changes, releasing pro-inflammatory cytokines, chemokines, and neurotoxic factors. These neurotoxic substances contribute to neuronal damage, synaptic dysfunction, and ultimately the impairment observed in HAND. While ART has revolutionized HIV treatment, emerging shreds of evidence suggest that certain drugs may contribute to neurodegeneration. Understanding the mechanisms and risk factors associated with ART-induced neurotoxicity is important for minimizing long-term neurological consequences. However, challenges persist in fully comprehending the interactions between microglia, HIV infection, and ART. This review comprehensively explores the significance of microglia in HAND also investigating the effects of ART on these neurological conditions, encompassing research on HIV, HAND, and the involvement of microglial senescence.