The CSF scRNA-Seq was performed longitudinally at baseline, post ramp-up with morphine (pre-infection), during acute infection, and after suppression of viremia to profile cell-specific transcriptomic signatures that mirror the CNS pathogenesis observed in opioid-dependent PWH.<h4>Results</h4>We observed the presence of all major immune cells in CSF, including CD4 + T<sub>CM</sub> cells, CD4 + T<sub>EM</sub> cells, CD8+ naïve T cells, CD8 + T<sub>CM</sub> cells, CD8 + T<sub>EM</sub> cells, CD14 + Monocytes, CD16 + Monocytes, NK cells, and B cells. Here, CD8A is linked to infection.