Circulating plasma protein biomarkers associated with risk of negative clinical outcomes in virally suppressed people with HIV receiving medications for opioid use disorder

Background Opioid use impairs immune response, but the mechanism of action underlying this effect remains unknown. In people with HIV-1 (PWH), including those on suppressive antiretroviral therapy (ART), opioid use may exacerbate chronic inflammation. To address this knowledge gap, we sought to identify immune biomarkers in virally suppressed PWH on medications for opioid use disorder (MOUD), including methadone (MET) and suboxone (SUB), and to assess possible associations with clinical outcomes. Methods The study enrolled PWH receiving ART from the Philadelphia FIGHT Treatment Center in three groups based on their medication regimen: control (no known opioid use, no MOUD, n = 14), SUB (n = 15), and MET (n = 14). Plasma samples were analyzed with the SomaScan platform for differentially expressed proteins. Based on protein signature modeling, SomaSignal tests were evaluated for clinically relevant information about participant health and risk status. Between-group differences were tested using Wilcoxon rank-sum test and beta regression; p values were adjusted for false discovery rate. Results The mean age of participants was 48.6 years and the mean ART duration was 10.4 years, showing consistency across all groups. However, the proportion of female participants was lower in the control group (14.3%) versus the SUB (40.0%) and MET (42.9%) groups. The SomaScan assay revealed 12 unique proteins, identified by 13 SOMAmers, that were differentially expressed between the control and MOUD groups. Specifically, PWH on MOUD exhibited higher levels of HSP70, KERA, NTR1, FLRT2, sCD14, SDF-1, IGLL1, AT1B2, and ROR1, while the control group had higher levels of MMAC, IGFALS, and ELA2A (p < 0.001). ELISA analysis corroborated the findings, showing that results for HSP70, IGLL1, and sCD14 were concordant with SomaScan results. SomaSignal tests indicated that PWH receiving MET had possible higher risks for kidney disease, heart failure, and dementia, alongside trends suggesting reduced visceral fat and alcohol impact versus other groups. The increased risks for kidney disease and dementia were confirmed using beta regression analysis. Conclusion These data suggest that PWH chronically exposed to MOUD have higher levels of circulating protein biomarkers that may be linked to increased risk of adverse clinical outcomes.