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Study Description

People living with HIV (PLWH) are at the higher risk for impaired cognitive functions such as HIV-Associated Neurocognitive Disorder or HAND. Further, higher use of legal and illegal opioids among PLWH could affect their immune functions and exacerbate CNS impairment. However, little is known about the HIV harboring cell types in brain, effect of ART on specific CNS cell types, and the modification of brain functions by opioid use. The human brain is composed of an enormous diversity of cell types defined by distinct gene expression, morphology, connectivity, and physiology. Single cell sequencing assays enable cell type-specific analysis of the role of these cell types in healthy brain function and disease. The overall objective of this proposal is to reveal the single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection using snRNA-seq and snATAC-seq technologies, bioinformatics approaches, and validation studies. Single cell and spatial characterization of HIV and opioid use disorder across multiple regions of the human brain will be performed. These regions may include nucleus accumbens (NAc), prefrontal cortex (PFC), cerebellum, amygdala, and other accessible regions. These results will provide an unprecedented conceptual and experimental system to identify single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection as well as potential opportunities to illuminate how genetic variation affects gene expression.

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Study Attribution
  • Principal Investigator
    • Tariq Rana. University of California, San Diego, San Diego, CA,USA.
  • Funding Source
    • U01DA053630. National Institutes of Health, Bethesda, MD, USA.