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<p>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 &lt; 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&#xa0;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.</p>

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Longitudinal plasma proteomic signatures of elite and viremic spontaneous HIV controllers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月22日

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  • 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

摘要

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.