PI-021 - THE EFFECTS OF OPIOIDS ON BLOOD-BRAIN BARRIER INTEGRITY, ANTIRETROVIRAL ACCUMULATION, AND NEUROINFLAMMATORY CHEMOKINE PROFILES IN ECOHIV-INFECTED MICE

A. Jones¹, K. Rademeyer¹, E. Miller², D. Conway³, J. McClay⁴, K. Hauser², M. McRae²; ¹Virginia Commonwealth University, Richmond, VA, United States, ²Virginia Commonwealth University, Richmond, VA, USA, ³Ohio State University, Columbus, OH, United States, ⁴Virginia Commonwealth University School of Pharmacy, Richmond, USA, USA.

Background: Comorbid opioid use disorder (OUD) and HIV worsen clinical outcomes due to increased neuroinflammation and blood-brain barrier (BBB) disruption. Fentanyl, a potent opioid, has distinct pharmacological properties compared to morphine, potentially altering neuroinflammatory responses and antiretroviral (ARV) drug penetration in the brain differently. This study compares the effects of fentanyl and morphine on tight junction protein expression, ARV accumulation, and chemokine profiles in EcoHIV-infected mice.

Methods: Male and female C57BL/6 mice were divided into groups receiving morphine, fentanyl, or saline with or without EcoHIV infection. The expression of tight junction proteins claudin-5 and ZO-1 was measured in striatum and hippocampus tissue using ELISA. ARV concentrations (abacavir, lamivudine, dolutegravir) were assessed using LC-MS/MS. Chemokine levels (CCL2, CCL3, CCL4, and CCL5) were analyzed using a multiplex assay.

Results: Both fentanyl and morphine reduced ARV brain concentrations in infected mice, but these effects were opioid- and region-specific. Fentanyl decreased dolutegravir in the hippocampus, while morphine decreased abacavir in the striatum. Fentanyl altered chemokine expression differently than morphine, significantly increasing CCL2 and CCL4 in the striatum, while reducing CCL3 in the hippocampus. Tight junction protein expression was also differentially affected; fentanyl exposure led to decreased ZO-1 in males but increased it in females. Claudin-5 expression was reduced in all fentanyl-treated groups, particularly in infected mice.

Conclusion: The distinct effects of fentanyl versus morphine on ARV penetration, chemokine profiles, and tight junction protein expression highlight the need for opioid-specific strategies in managing neuroinflammatory and barrier integrity issues in people with HIV. Fentanyl’s unique impact suggests it may exacerbate neuroHIV-related pathology more than other opioids, underscoring the importance of tailored clinical approaches for patients with OUD.