Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence

HIV-1 remains a major global health concern, exerting detrimental effects not only on the immune system but also on the central nervous system (CNS). Soon after HIV-1 infection, the virus can breach the blood-brain barrier (BBB), initiating processes that result in neuronal damage and cell death. These effects manifest clinically as a spectrum of cognitive, behavioural, and motor impairments collectively termed HIV-associated neurocognitive disorders (HAND). Among the viral proteins implicated in CNS pathology, the Trans-Activator of Transcription (Tat) protein stands out due to its pronounced neurotoxic and neurotropic characteristics. Tat is secreted by infected cells and can accumulate in the CNS, persisting even in individuals undergoing effective antiretroviral therapy (ART), thereby contributing to ongoing neurocognitive complications. Although Tat has been extensively studied since the 1980s, current literature examining its effects within the context of modern treatment regimens remains sparse. This chapter offers a comprehensive and updated review of the role of HIV-1 Tat in neuropathogenesis, drawing on research from the past 25 years to highlight its contribution to HAND and to outline potential avenues for therapeutic advancement.