Longitudinal plasma proteomic signatures of elite and viremic spontaneous HIV controllers
Year: 2026
Type: article
Study design: Observational Study
Abstract: A small percentage of people living with HIV (PLHIV) spontaneously regulate viral replication without suppressive antiretroviral treatment (ART) and are categorized into ‘elite controllers’ (EC, HIV-RNA < 50 c/mL) and ‘viremic controllers’ (VC, HIV-RNA between 50-10,000 c/ml). Some EC and VC may lose controller status in time. Here we provide extensive plasma proteomics to identify biomarkers and pathways related to spontaneous viral control and its long-term preservation among 36 EC and 147 VC (discovery) and 14 EC and 5 VC (validation). VC exhibited higher concentrations of CRTAM, LY9, and CD6 and lower concentrations of VAT1 compared to EC in both the discovery and validation cohort. Longitudinal analysis of pre- and post-ART samples (median follow-up: 5.3 years) revealed downregulation of various immune-related proteins in both EC and VC. Over a 17-year follow-up period, loss of viral control occurred in 31% of VC and 3% of EC. T-cell associated proteins (CRTAM, LY9, CD6), along with ICAM3, SH2D1A, C1QL2, and CNGB3, predicted loss of viral control years before its occurrence. Markers of chronic immune activation (sPD-L1, sCD25, IL-10, TGF-β, IFN-γ, and TNF-α) and systemic inflammation (TNF, IL-1β, IL-6, and sCD14) were not predictive. Our findings underscore the dynamic interplay between T cell function and viral replication in maintaining HIV control and identify key biomarkers that predict viral load surges. Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.
Source: Nature Communications
Authors: Nadira Vadaq, Albert L. Groenendijk, Jéssica C. dos Santos, Kavita Mehta, Ferdinand W.N.M. Wit, Wilhelm A. J. W. Vos, Martinus J. T. Blaauw, Louise E. van Eekeren, Laurens Lambrechts, Sofie Rutsaert, Erni J. Nelwan, Cheng-Jian Xu, Leo A. B. Joosten, Quirijn de Mast, Vasiliki Matzaraki, Jan van Lunzen, Casper Rokx, Annelies Verbon, Mihai G. Netea, Linos Vandekerckhove, André J. A. M. van der Ven
Institutions: Radboud University Nijmegen, Radboud University Medical Center, Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo, Erasmus MC, Ghent University, Stichting HIV Monitoring, OLVG, Elisabeth-TweeSteden Ziekenhuis, University of Indonesia, Medizinische Hochschule Hannover, Helmholtz Centre for Infection Research, Centre for Individualised Infection Medicine, Center for Experimental and Clinical Infection Research, Erasmus University Rotterdam, University of Bonn
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7125400865