---
title: "Opioid-use disorder Linked to Persistent Immune Dysregulation in People Living with HIV"
id: "biorxiv-20-chronic-opioid-associated-immune-dysregulation-among-people-living-with-hiv"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-20-chronic-opioid-associated-immune-dysregulation-among-people-living-with-hiv"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.31.748399v1?rss=1"
published_at: "2026-09-03T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Opioid-use disorder Linked to Persistent Immune Dysregulation in People Living with HIV
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-20-chronic-opioid-associated-immune-dysregulation-among-people-living-with-hiv
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.31.748399v1?rss=1)
- **Published At:** 2026-09-03T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Researchers studied people living with HIV (PWH) who had opioid-use disorder (OUD) and measured immune function over 6 months of optimized antiretroviral therapy (ART). - The study longitudinally sampled peripheral blood from PWH with OUD (PWH/OUD+) at months 0, 3, and 6 while a reference cohort of PWH without OUD (PWH/OUD−) with suppressed viral load provided a single sample. - Despite ART-mediated reductions in HIV viral load (VL), PWH/OUD+ showed persistent systemic immune abnormalities compared with the reference cohort. - Elevated plasma markers in PWH/OUD+ included **sCD163**, **sCD14**, fractalkine, and I-TAC; TGF-β1 levels were reduced. - Cellular alterations in PWH/OUD+ included expansion of **CD16⁺ monocytes** and changed expression of CCR2, CD38, and CD11b. - Lymphoid compartments (CD4⁺ and CD8⁺ T cells), NK cells, and B cells also demonstrated persistent changes in activation, metabolism, and trafficking markers among PWH/OUD+. - Monocytes from PWH/OUD+ had attenuated cytokine responses to lipopolysaccharide (LPS) stimulation, indicating impaired innate responsiveness. - Mixed-effects models adjusted for HIV VL and VL-stratified analyses were used to assess associations; findings suggest opioid exposure is independently associated with chronic immune dysregulation in PWH. - Authors conclude that OUD may contribute to sustained inflammation, immune dysfunction, and could promote long-term HIV-associated comorbidities despite viral suppression with ART. - Funding sources and competing interest disclosures were reported; the authors declared no competing interests and listed NIH grants supporting the work.
## Clinical Analysis & Structured Key Points
Chronic opioid-associated immune dysregulation among people living with HIV | bioRxiv Skip to main content New Results Chronic opioid-associated immune dysregulation among people living with HIV View ORCID Profile Brent Bever , Michelle Underwood , Byung Park , Susan Pereira Ribeiro , Ryan R Cook , Lynn Kunkel , P. Todd Korthuis , View ORCID Profile Christina Lancioni doi: https://doi.org/10.64898/2026.08.31.748399 Brent Bever 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Brent Bever Michelle Underwood 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Byung Park 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Susan Pereira Ribeiro 2 Emory University School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ryan R Cook 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lynn Kunkel 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site P. Todd Korthuis 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Christina Lancioni 1 Oregon Health and Science University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christina Lancioni For correspondence: lancioni{at}ohsu.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Objectives: Persistent immune dysregulation contributes to chronic disease among people living with HIV (PWH), even after viral suppression with antiretroviral therapy (ART). Although chronic opioid exposure is associated with adverse clinical outcomes, its impact on immune homeostasis during ART remains incompletely understood. We investigated whether opioid use disorder (OUD) is associated with persistent systemic and cellular immune dysregulation despite ART-mediated reductions in HIV viral load (VL). Methods: Peripheral blood was collected longitudinally from PWH with OUD (PWH/OUD+) and detectable HIV VL during 6 months of optimized ART (months 0, 3, and 6). A reference cohort of PWH without OUD (PWH/OUD−) and suppressed HIV VL provided a single blood sample. Immune profiling included plasma inflammatory biomarkers, multiplex cytokine analyses, spectral flow cytometry, and assessment of monocyte cytokine responses following lipopolysaccharide (LPS) stimulation. Mixed-effects models adjusted for HIV VL and VL-stratified analyses were performed. Results: PWH/OUD+ exhibited persistent immune dysregulation despite reductions in HIV VL. Plasma sCD163, sCD14, fractalkine, and I-TAC remained elevated, whereas TGF-β1 was reduced. OUD was associated with expansion of CD16⁺ monocytes and altered expression of CCR2, CD38, and CD11b. CD4⁺ and CD8⁺ T cells, NK cells, and B cells also exhibited persistent alterations in markers of activation, metabolism, and trafficking. Monocytes from PWH/OUD+ displayed attenuated cytokine responses following LPS stimulation. Conclusions: OUD is associated with persistent systemic and cellular immune dysfunction in PWH despite ART-mediated viral suppression, supporting opioid exposure as an independent contributor to chronic immune dysregulation that may promote inflammation, immune dysfunction, and long-term HIV-associated comorbidities. Keywords: HIV, Opioid-use disorder, innate immunity, cytokine Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Health , UG1DA015815, UG1DA013732, R03DA039731, R01DA046229 and R36DA061652 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted September 03, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Chronic opioid-associated immune dysregulation among people living with HIV Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Chronic opioid-associated immune dysregulation among people living with HIV Brent Bever , Michelle Underwood , Byung Park , Susan Pereira Ribeiro , Ryan R Cook , Lynn Kunkel , P. Todd Korthuis , Christina Lancioni bioRxiv 2026.08.31.748399; doi: https://doi.org/10.64898/2026.08.31.748399 Share This Article: Copy Citation Tools Chronic opioid-associated immune dysregulation among people living with HIV Brent Bever , Michelle Underwood , Byung Park , Susan Pereira Ribeiro , Ryan R Cook , Lynn Kunkel , P. 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