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Publication
bioRxiv

Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection

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  • May 1, 2026
  • Benjamin Bimber, et al., Oregon Health and Science University
Topic/Product:
Immunology, Inflammation, Inflammation Panel 250
Disease Area:
SIV
Sample Type:
Plasma-NHP

Abstract

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can face non-AIDS complications, partially driven by chronic immune activation. To define immune perturbations during ART-suppressed viral infection, we performed longitudinal single-cell transcriptomic and plasma proteomic analysis of rhesus macaques infected with SIVmac239M and ART-treated for 70 weeks. We identified broad, bi-phasic immune changes. Acute infection involves an interferon-driven signature, correlated with viral replication, that largely resolves with viral control. Cell-associated virus correlated with interferon-stimulated genes in most tissues; however, this was blunted in gut-associated lymph nodes, a feature that may contribute to reservoir persistence. Separate alterations manifest 54-66 weeks-post-infection, after 40 weeks of viral suppression, including broad TGF-β and NF-kB signaling and discrete bursts of inflammatory monocytes, largely restricted to bone marrow. These data highlight the biphasic remodeling of long-term ART-suppressed HIV, identifying specific tissues and cell populations with dysregulation, with implications for the treatment of PLWH.

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Authors & Affiliations

Maanasa Kaza¹, Benjamin Varco-Merth², GW McElfresh¹, Sebastian Benjamin¹, Gregory J. Boggy¹, Morgan Chaunzwa¹, Shana Feltham², Sohita Ojha², Karina Belica², Andrea N. Selseth², Michael Nekorchuk², Kathleen Busman-Sahay², Brandon F. Keele³, Dan H. Barouch⁴⁵, Jeffrey D. Lifson³, Jacob D. Estes², Scott G. Hansen¹², Afam Okoye², Louis J. Picker¹², and Benjamin N. Bimber* ¹²

¹ Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
² Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
³ AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
⁴ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.