Janani Madhuravasal Krishnan

Background: The United States continues to experience a major drug epidemic driven by synthetic opioids, particularly fentanyl. Emerging evidence suggests that opioids alter immune responses and viral pathogenesis. This study evaluated inflammatory and apoptotic markers among individuals living with HIV and/or hepatitis C virus (HCV) infection in the context of opioid/fentanyl exposure. Methods: Whole blood was collected from adults with HIV, HCV, and/or opioid use disorder (OUD), along with healthy controls. Plasma toxicology screening for illicit substances was performed using LC-MS/MS. Inflammatory cytokines and chemokines (IL-6, IL-8, SDF-1α, MIP-1α, MIP-1β, RANTES, and TNF-α) were measured by Luminex, and M30 was measured by ELISA. Biomarkers were compared using the Kruskal–Wallis test, with multivariable regression used to identify independent associations. Results: Among 98 participants, 37.8% had OUD, 53.9% had a history of injection drug use, and 95.9% of toxicology-confirmed opioid users tested positive for fentanyl. Participants with HIV had higher RANTES and lower M30 levels, whereas participants with HCV had higher IL-8, MIP-1β, TNF-α, and M30 levels and lower RANTES. Multivariable analysis identified independent associations of IL-8 with HIV and HCV status, SDF-1α with injection drug use and recent fentanyl exposure, and MIP-1β with HCV status. The number of substances detected was not independently associated with inflammatory marker levels. Conclusions: HIV and HCV were associated with distinct inflammatory and apoptotic profiles in the setting of widespread fentanyl exposure, suggesting that chronic viral infection and opioid exposure contribute to immune dysregulation and may influence disease progression.

Background: In the United States, the illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis. Synthetic opioids are known to enhance viral replication and to suppress immunologic responses, but their effects on HIV pathogenesis remain unclear. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types. Methods: TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at varying concentrations. Expression levels of the CXCR4 and CCR5 chemokine receptors and HIV p24 antigen were quantified with ELISA. HIV proviral DNA was quantified using SYBR RT-PCR. Cell viability was detected with the MTT assay. RNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Results: Fentanyl enhanced expression of both chemokine receptor levels in a dose-dependent manner in HIV-susceptible and infected cell lines. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral/interferon response, chemokine signaling, and NFκB signaling were differentially regulated. Conclusions: Synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression. Increased virus levels suggest that opioid use may increase the likelihood of transmission and accelerate disease progression.