AUTHOR=Krishnan Janani Madhuravasal , Roskin Krishna M. , Meeds Heidi L. , Blackard Jason T. 

TITLE=Effect of fentanyl on HIV expression in peripheral blood mononuclear cells

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1463441

DOI=10.3389/fmicb.2024.1463441

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4<sup>+</sup> T lymphocytes.</p></sec><sec><title>Methods</title><p>CD4<sup>+</sup> T lymphocytes from HIV-negative donors were activated, infected with HIV<sub>NL4-3</sub>, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes.</p></sec><sec><title>Results</title><p>Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4<sup>+</sup> T lymphocytes.</p></sec><sec><title>Discussion</title><p>The results of our findings suggest that fentanyl promotes HIV replication <italic>ex vivo</italic>, emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.</p></sec>