PI-018 - INTERPLAY BETWEEN HIV AND METHADONE: EFFECTS ON CHEMOKINE DYSREGULATION AND NEUROINFLAMMATION.

T. Halsey¹, K. Rademeyer², M. McRae³; ¹Virginia Commonwealth University School of Pharmacy, Richmond, VA, United States, ²Virginia Commonwealth University, Richmond, VA, United States, ³Virginia Commonwealth University, Richmond, VA, USA.

Background: HIV infection and opioid use disorder (OUD) often co-occur, with opioids exacerbating HIV-related neuroinflammation. Chemokines, regulators of immune cell trafficking and activation, mediate this inflammation. Methadone, while effective for OUD treatment, is an opioid that may contribute to neuroinflammation in HIV patients. This study examines methadone’s impact on chemokine dysregulation in the striatum and hippocampus, exploring the interaction between HIV, opioids, and neuroinflammation.

Methods: HIV-1 Tat transgenic female mice (n = 36) were divided into four groups: Tat-/placebo, Tat-/methadone, Tat+/placebo, and Tat+/methadone. Following a 14 day induction of Tat, a neurotoxic HIV protein, methadone (25 mg/kg/day) or placebo was administered via osmotic pumps for 5 days. Chemokine levels were measured using a LegendPlex panel. Data were analyzed with Kruskal-Wallis tests, Dunn’s post-hoc tests, and exploratory principal component analysis (PCA).

Results: Tat and methadone exposure significantly altered chemokine expression, particularly in the striatum. Striatal PCA identified four key chemokines - CCL11, CCL17, CXCL1, and CCL22 - as drivers of group separations by opioid and Tat status. Kruskal-Wallis and Dunn’s tests confirmed dysregulation of these chemokines. CCL11, CCL17, and CXCL1 showed the most significant dysregulation in the Tat+/Methadone group, suggesting additive effects of Tat and methadone. CCL22 was primarily influenced by methadone, with both Tat-/Methadone and Tat+/Methadone groups showing dysregulation. In contrast, the chemokine changes in the hippocampus were less distinct. The PCA showed no clear group separation, which highlights the regional specificity of chemokine dysregulation in the brain.

Conclusion: These data suggest that the HIV-methadone interplay may result in exacerbation of neuroinflammation. Further, although methadone is an effective treatment for OUD, our findings indicate methadone may actually have unintended consequences on immune dysregulation in the brain, especially in people living with HIV. Future studies should examine methadone’s effects on other aspects of HIV neuropathology to more fully elucidate its impact within the brain.