# Early Transcriptomic Signatures of Immune Response Modulation Following Antiretroviral Therapy in HIV-Infected Patients

## TL;DR

This study examines how gene activity in immune cells changes early after HIV patients start antiretroviral therapy, revealing a decrease in chronic immune activation.

## Contribution

The study provides new insights into early transcriptomic changes in immune response following ART initiation in HIV patients.

## Key findings

- 87 differentially expressed genes were identified, including 67 downregulated interferon-stimulated genes.
- Functional analysis showed suppression of type I interferon and antiviral signaling pathways after ART.
- PCA and clustering revealed a distinct post-ART transcriptional shift in immune cells.

## Abstract

Human immunodeficiency virus (HIV) remains a global public health challenge. Antiretroviral therapy (ART) improves outcomes by suppressing viral replication and enabling immune recovery, yet the early molecular mechanisms of immune-related transcriptional change after ART remain insufficiently characterized. We enrolled eight ART-naïve male patients with HIV aged 18–35. Peripheral blood mononuclear cells (PBMCs) were collected before and after 24 weeks of combination ART (TDF, 3TC, DTG) and underwent bulk RNA-seq (Illumina HiSeq 1500, Illumina, Inc., San Diego, CA, USA). Differential expression was assessed with DESeq2 (paired design); gene set enrichment analysis (GSEA), principal component analysis (PCA), hierarchical clustering, and protein–protein interaction (PPI) networks (STRING/NetworkX) explored functional patterns and transcriptomic shifts. We identified 87 differentially expressed genes, including 67 downregulated interferon-stimulated genes (e.g., IFI44L, ISG15, STAT1) and 20 upregulated transcripts, mostly pseudogenes related to ribosomal proteins. Functional enrichment revealed suppression of type I interferon and other antiviral signaling pathways. PCA and hierarchical clustering indicated a post-ART transcriptional shift. These findings suggest that early immune recovery following ART involves downregulation of chronic interferon-driven activation. This observation may correspond to partial restoration of T-cell functional capacity, reduced immune exhaustion, and a rebalanced antiviral immune environment.