The Genetic Fingerprint of HIV in the Brain: Insights into Neurocognitive Dysfunction

HIV, primarily targeting CD4 cells, infiltrates the CNS through various mechanisms, including chemokine-mediated signaling and disruption of the blood-brain barrier, leading to neuroinflammation and neuronal dysfunction. Viral proteins such as gp120, Tat, and Vpr directly induce neurotoxicity, oxidative stress, and mitochondrial dysfunction, exacerbating cognitive deficits and motor impairments observed in HIV-associated neurocognitive disorders (HAND). Host genetic factors, including CCR5 mutations and HLA alleles, influence susceptibility to HIV-related neurologic complications, shaping disease progression and treatment responses. Advanced molecular and bioinformatics techniques, from genome sequencing to structural modeling and network analysis, provide insights into viral pathogenesis and identify potential therapeutic targets. These findings underscore the future potential of precision medicine approaches tailored to individual genetic profiles to mitigate neurologic complications and improve outcomes in HIV-infected populations. This comprehensive review explores the intricate interplay between HIV infection and neurogenetics, focusing on how the virus impacts the central nervous system (CNS) and contributes to neurocognitive disorders. This report delves into how the virus influences genetic expression, neuroinflammation and neurodegeneration, offering insights into molecular mechanisms behind HAND.