Pro-Inflammatory Markers in Persons Living with HIV and HCV: The Role of Opioid Use

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.