Review Article Volume 7 • Issue 3 408 Affiliation: HIV Drug Resistance Laboratory, The National Institute of Translational Virology and AIDS Research (formerly National AIDS Research Institute NARI), Pune-411026, India *Corresponding author: Swarali N. Kurle, HIV Drug Resistance Laboratory, The National Institute of Translational Virology and AIDS Research (formerly National AIDS Research Institute NARI), Pune-411026, India. Citation: Pratiksha S. Pansambal and Swarali N. Kurle. Unveiling the Role of Microglia in HIV- Associated Neurodegeneration: Current Insights and Future Directions. Fortune Journal of Health Sciences. 7 (2024): 408-417. Received: June 26, 2024 Accepted: July 05, 2024 Published: July 30, 2024 Unveiling the Role of Microglia in HIV-Associated Neurodegeneration: Current Insights and Future Directions Pratiksha S. Pansambal and Swarali N. Kurle* Abstract 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. Keywords: HIV, Neurodegeneration, Microglia, ART, Senescence Introduction HIV, the most enduring pandemic in history, has had a profound impact on mil-lions of individuals globally. It can be found in nearly all parts of the body, including the CNS, where it enters shortly after infection and infects brain cells [1] With advancements in ART, HIV has become a lifelong manageable chronic disease. Combination ART (cART), which includes drugs inhibiting critical HIV enzymes such as integrase, reverse transcrip- tase, and protease, has proven quite effective [2]. While ART has reduced mortaity rates, it cannot eliminate latent HIV from the reservoirs including the Blood Brain Barrier (BBB). The BBB confines drug permeability into the CNS. Low drug concentrations may lead to ineffective control of HIV leading to neurocognitive dysfunction in many individuals with HIV receiving ART [3-5]. HIV infection persists in brain cells and makes it difficult to eradicate. Entry of HIV into CNS The BBB serves as a protective wall that prevents the entry of harmful