Single cell RNA transcriptome response to fentanyl use in persons with HIV infection

The US is experiencing a major drug epidemic largely attributed to synthetic opioids including fentanyl. We considered how illicit fentanyl use in persons living with HIV impacted gene expression profiles in the peripheral blood. Whole blood was collected from 10 HIV-positive adults with a diagnosis of opioid use disorder (OUD) and 7 HIV-positive non-opioid using controls. Mean HIV viral loads were higher for the OUD+ group, although this difference did not reach statistical significance (2.44 versus 1.00 log10 copies/mL; p = 0.12; two-sample T test). 216,641 cells were evaluated by single cell RNAseq. Cell frequencies were not different by opioid status except for NK cells (lower for opioid use; p = 0.0045). For CD4+ T lymphocytes, 10 differentially expressed genes (DEGs) were higher and 8 were lower in opioid-positive persons. In CD8+ T lymphocytes, there were 15 higher and 13 lower DEGs for opioid-positive study participants. In monocytes, 72 DEGs were higher and 37 DEGs were lower in opioid-positive participants. In B lymphocytes, 17 DEGs were higher and 10 were lower in opioid-positive versus opioid-negative participants. These findings highlight multiple pathways by which opioid use may contribute to HIV pathogenesis. Rigorous characterization of the interactions among HIV, opioids, and host cells can improve clinical management paradigms, facilitate rational public health policies, and reveal additional pathways for novel target-specific therapeutic interventions.