Fentanyl‐Induced Changes in the Cellular Transcriptome of a Person Living With HIV: A Case Report

The US is experiencing a major drug epidemic attributed in large part to synthetic opioids such as fentanyl. Opioid receptors exist on multiple immune cell types and alter innate and adaptive immune functions. Opioids also promote viral replication and accelerate disease pathogenesis. We previously reported that fentanyl resulted in significantly elevated levels of HIV replication and chemokine coreceptor expression in a dose‐dependent manner in lymphocytes and monocyte‐derived macrophages. Cell type‐specific data on the regulation of cellular processes by fentanyl are rare. Here, we considered how physician‐prescribed fentanyl impacted gene expression profiles in the peripheral blood of a person living with HIV. He was diagnosed with septic bursitis and underwent operative incision and debridement. 15,834 and 15,642 (99.2%) cells were evaluated by single cell RNAseq analysis of pre‐ and postfentanyl blood samples. There were 133 differentially expressed genes (DEGs) in CD4 + T lymphocytes between the pre‐ and postfentanyl blood samples. There were 136 DEGs in CD8 + T lymphocytes, 74 DEGs in B lymphocytes, 180 DEGs in monocytes, 355 DEGs in dendritic cells, and 144 DEGs in NK cells. Biological processes that were enriched in multiple peripheral blood cell types included those associated with coronavirus disease, NFκB signaling, TNF signaling, and IL‐17 signaling. This case study highlights multiple pathways by which opioids 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.