Immune Network Dysregulation of the Central Nervous System with HIV Persistence and Opioid Abuse

HIV persists within the central nervous system, despite successful suppression of viral replication with antiretroviral therapy, leading to incomplete viral eradication, as well as HIV-associated neurocognitive disorder that is further exaggerated by opioid abuse. Yet, the underlying molecular and cellular mechanisms remain the mystery. We employ state-of-the-art and novel methodologies in neuroscience, immunobiology, and computational biology to dissect the dysregulated immune network in the central nervous system of individuals with HIV infection with and without opioid exposure at the single-cell level and the cell-type-specific response to opioids in the context of HIV. This study will open up new vistas in the important area of HIV persistence and neuroinflammation in the central nervous system, and may provide additional, foundational knowledge for the development of future therapeutics to treat HIV in individuals with and without opioid use disorder.