Single cell opioid (fentanyl) responses in the context of HIV

Abstract The number of drug overdose deaths has increased significantly in recent years. By 2019, 70.6% of drug overdose deaths involved opioids, and in Ohio, >90% of unintentional overdose deaths involved fentanyl. Opioid receptors are expressed in multiple peripheral blood mononuclear cell (PBMC) types that are susceptible to HIV infection but poorly studied, particularly in those with HIV and fentanyl use. We previously identified multiple differentially expressed genes related to apoptosis, antiviral/interferon response, chemokine signaling, NFκB signaling, viral gene expression, and hepatocarcinogenesis that were differentially regulated in the presence/absence of fentanyl in several cell types in vitro. In a separate NIDA- funded R61/R33 focused on fentanyl and viral infections, we collected peripheral blood samples from >100 persons with HIV and/or HCV and active drug use, as well as healthy controls. Using a novel liquid chromatography-tandem mass spectrometry-based approach, fentanyl was detected in 100% of patients presenting with opioid overdose. Single cell transcriptome analysis identified multiple differentially expressed genes in fentanyl-positive versus fentanyl-negative participants in CD4+ and CD8+ T lymphocytes, monocytes, B lymphocytes, dendritic cells, and natural killer cells. Translational research on opioid-cell and opioid-virus interactions is essential for optimized treatment and limiting viral reactivation. Thus, we propose a multi-omics approach and complementary in vivo and ex vivo studies in well-characterized patient cohorts to directly evaluate the impact of fentanyl on markers of the single cell transcriptome and microRNA profile.