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Published on: March 5, 2022
Distinct Transcriptomic Profiles in ART-Treated People with HIV Are Associated with NF-κB-regulated Gene Expression
Yingfan Wang1, German G Gornalusse2,3, Urja Bhatt4
1Department of Computer Science, Duke University, Durham, North Carolina, United States of America.
Journal of Acquired Immune Deficiency Syndromes (1999)
|July 27, 2026
Summary
People with HIV on effective antiretroviral therapy (ART) show distinct CD4+ T cell gene expression patterns linked to inflammation. These immune signatures may help stratify patients and understand ongoing immune dysfunction despite viral suppression.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent immune dysregulation and elevated morbidity.
- Understanding transcriptomic heterogeneity in CD4+ T cells is crucial for identifying immune signatures in ART-treated PWH.
Purpose of the Study:
- To define transcriptomic heterogeneity in peripheral CD4+ T cells of ART-treated PWH.
- To identify immune signatures associated with clinical stratification in this population.
Main Methods:
- Bulk RNA sequencing of CD4+ T cells from 154 ART-treated PWH.
- Analysis of plasma cytokine levels.
- Application of Pairwise Controlled Manifold Approximation (PaCMAP) for transcriptomic clustering and association with clinical/immunological parameters.
Main Results:
- PaCMAP identified three distinct transcriptomic clusters.
- Clusters showed enrichment for NF-κB-regulated genes, indicating chronic immune activation.
- Clusters were modestly associated with CD4:CD8 ratio and differed in plasma IL-1β, TNF-α, and G-CSF levels.
Conclusions:
- Distinct transcriptomic subgroups exist in ART-treated PWH, characterized by NF-κB-driven gene expression and inflammatory profiles.
- These immune signatures could serve as biomarkers for immunological stratification.
- Findings offer insights into persistent immune dysfunction despite viral suppression.
