Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

Opioid use has negative effects on immune responses and may impair immune reconstitution in persons living with HIV (PLWH) infection undergoing antiretroviral treatment (ART). The effects of treatment with μ opioid receptor (MOR) agonists (e.g., methadone, MET) and antagonists (e.g., naltrexone, NTX) on immune reconstitution and immune activation in ART‐suppressed PLWH have not been assessed in‐depth. We studied the effects of methadone or naltrexone on measures of immune reconstitution and immune activation in a cross‐sectional community cohort of 30 HIV‐infected individuals receiving suppressive ART and medications for opioid use disorder (MOUD) (12 MET, 8 NTX and 10 controls). Plasma markers of inflammation and immune activation were measured using ELISA, Luminex, or Simoa. Plasma IgG glycosylation was assessed using capillary electrophoresis. Cell subsets and activation were studied using whole blood flow cytometry. Individuals in the MET group, but no in the NTX group, had higher plasma levels of inflammation and immune activation markers than controls. These markers include soluble CD14 (an independent predictor of morbidity and mortality during HIV infection), proinflammatory cytokines, and proinflammatory IgG glycans. This effect was independent of time on treatment. Our results indicate that methadone‐based MOUD regimens may sustain immune activation and inflammation in ART‐treated HIV‐infected individuals. Our pilot study provides the foundation and rationale for future longitudinal functional studies of the impact of MOUD regimens on immune reconstitution and residual activation after ART‐mediated suppression. Graphical Long‐term exposure to methadone may sustain immune activation and inflammation in ART‐treated HIV‐infected individuals, impairing their immune reconstitution outcomes.