Poster #82: Ekaterina Shipilova Luis Montaner MS

Metabolic Reprogramming in ART-suppressed PLWH: Exacerbation by Medications for Opioid Use Disorder

Ekaterina Shipilova¹, Livio Azzoni¹, Andrew Kossenkov¹, Aaron R. Goldman¹, Matthew Fair¹, Karam Mounzer², Emily Hiserodt², Rachel Holbert³, Amy D. Jessop³, Luis J. Montaner¹ ¹HIV Cure and Viral Diseases Center, The Wistar Institute, Philadelphia, PA ²Philadelphia FIGHT Community Health Centers, Philadelphia, PA ³Prevention Point Philadelphia, Philadelphia, PA

People living with HIV (PLWH) experience persistent metabolic alterations despite antiretroviral therapy (ART). Medications for opioid use disorder (MOUD; methadone and buprenorphine) may induce immunomodulatory effects and metabolic reprogramming in ART-suppressed PLWH. Study Design & Methods: This was a cross-sectional observational cohort study. Plasma samples were collected from a total of 194 participants: ART-suppressed PLWH (HIV; n=57), ART-suppressed PLWH receiving MOUD (HIV-MOUD; n=31), and healthy controls (CTRL; n=106). The cohort included 43.8% females and 53.1% non-White participants. Untargeted high-throughput metabolomics was performed by flow-injection mass spectrometry (General Metabolics, Inc.). A total of 1,331 m/z features were detected. Statistical comparisons between groups used two-sided Welch’s t-tests with Benjamini–Hochberg false discovery rate (FDR) correction. Pathway enrichment was performed with MetaboAnalyst 6.0 (MSEA-QEA) and Ingenuity Pathway Analysis (IPA). Results: In HIV versus CTRL, the most significant enrichment was in androgen/estrogen metabolism, with sulfated steroids (DHEA-S, androsterone sulfate) significantly reduced. In HIV-MOUD versus HIV, MOUD exposure further suppressed sulfated steroids and testosterone. Zeta-carotene was consistently reduced across comparisons, suggesting impaired antioxidant capacity. IPA confirmed overlapping disruptions and highlighted pathways related to inflammation, endocrine function, and gastrointestinal disease. Conclusions: This completed study demonstrates that ART-suppressed PLWH show metabolic reprogramming characterized by steroid hormone disruption, which is exacerbated by MOUD exposure. Sulfated steroids emerge as key metabolic signatures with implications for immune and systemic health.