GEO series
Continuous NRTI-based antiretroviral therapy induces progressive senescence-like reprogramming of alveolar macrophages [snMultiomics]
GSE307326
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing
32 samples
Submitted 2026/05/15
Platform GPL33758
Summary
Background: Advances in antiretroviral therapy (ART) have substantially improved the lives of people with HIV (PWH) and reduced HIV acquisition through pre-exposure prophylaxis (PrEP). However, the long-term effect of ART on the physiological state of cells remains poorly understood. Despite the success of ART in preventing the progression of HIV infection to AIDS, the aging PWH are suffering from a disproportional burden of non-AIDS comorbidities, including lung diseases. Methods: Given the central function of alveolar macrophages (AM) in pulmonary immunity, we evaluated the impact of nucleoside reverse transcriptase inhibitors (NRTI) based ART on AM of PWH and people on PrEP. We employed a retrospective cross-sectional design and evaluated the effects of continuous exposure to ART in the epigenetic and transcript of AM at bulk and single-nucleus multiomics levels. Results: We showed that continuous NRTI-based ART induces a progressive senescence-like pro-inflammatory state in AM, characterized by increased constitutive epigenetic and transcriptomic priming of genes involved in cell cycle arrest (e.g., CDKN1A/p21), components of the senescence-associated secretory phenotype (e.g., IL1A, IL6R, and CXCL8), as well as transcription factors subunits of the AP-1 family (e.g., FOSL1, JUN). At the AM single nucleus level we described a coordinated gene regulatory network linking key pro-inflammatory transcription factors to the transcriptomic alterations induced by ART. The senescence ART-linked epigenetic and transcriptomic changes were strongly dependent on the duration of ART and irrespective of HIV infection. A secondary time independent ART effect was observed for interferon signaling genes. This effect was more pronounced in people on PrEP and impaired AM response to ex vivo challenge with SARS-CoV-2. Conclusion: Combined, our data indicate that continuous NRTI-based ART promotes a dysregulated physiological state in AM, potentially contributing to age-related pulmonary comorbidities in PWH, such as COPD, pulmonary fibrosis, and asthma. PrEP is critically important for preventing HIV acquisition in the most vulnerable populations. By identifying therapeutical gaps in ART our study advocates for optimized or adjuvant therapies to prevent or mitigate potential long-term adverse effects of PrEP and to continuously improve the quality of life of PWH.
Published in
Fava VM, Dallmann-Sauer M, Orlova M et al.
· Frontiers in immunology 2026
· PMID 42099614
· doi:10.3389/fimmu.2026.1805936
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE307326_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 32 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1315233 and SRA study SRP617586. Searching any of these in the dataset finder brings you back here.
Study design
32 conditions, each sampled once — no replicated groups
Read from 32 sample titles: 32 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM9222110 Multiome, AMV3_snRNA, PWH, Unstimulated
- GSM9222111 Multiome, AMV3_snATAC, PWH, Unstimulated
- GSM9222112 Multiome, AMV3_SARS_snRNA, PWH, SARS-CoV-2 in vitro
- GSM9222113 Multiome, AMV3_SARS_snATAC, PWH, SARS-CoV-2 in vitro
- GSM9222114 Multiome, AMV23_snRNA, PWH, Unstimulated
- GSM9222115 Multiome, AMV23_snATAC, PWH, Unstimulated
- GSM9222116 Multiome, AMV23_SARS_snRNA, PWH, SARS-CoV-2 in vitro
- GSM9222117 Multiome, AMV23_SARS_snATAC, PWH, SARS-CoV-2 in vitro
- GSM9222118 Multiome, AMV11_snRNA, PWH, Unstimulated
- GSM9222119 Multiome, AMV11_snATAC, PWH, Unstimulated
- GSM9222120 Multiome, AMV11_SARS_snRNA, PWH, SARS-CoV-2 in vitro
- GSM9222121 Multiome, AMV11_SARS_snATAC, PWH, SARS-CoV-2 in vitro
- GSM9222122 Multiome, AMP36_snRNA, PrEP, Unstimulated
- GSM9222123 Multiome, AMP36_snATAC, PrEP, Unstimulated
- GSM9222124 Multiome, AMP36_SARS_snRNA, PrEP, SARS-CoV-2 in vitro
- GSM9222125 Multiome, AMP36_SARS_snATAC, PrEP, SARS-CoV-2 in vitro
- GSM9222126 Multiome, AMP32_snRNA, PrEP, Unstimulated
- GSM9222127 Multiome, AMP32_snATAC, PrEP, Unstimulated
- GSM9222128 Multiome, AMP32_SARS_snRNA, PrEP, SARS-CoV-2 in vitro
- GSM9222129 Multiome, AMP32_SARS_snATAC, PrEP, SARS-CoV-2 in vitro
- GSM9222130 Multiome, AMP23_snRNA, PrEP, Unstimulated
- GSM9222131 Multiome, AMP23_snATAC, PrEP, Unstimulated
- GSM9222132 Multiome, AMP23_SARS_snRNA, PrEP, SARS-CoV-2 in vitro
- GSM9222133 Multiome, AMP23_SARS_snATAC, PrEP, SARS-CoV-2 in vitro
- GSM9222134 Multiome, AMC38_snRNA, HC, Unstimulated
- GSM9222135 Multiome, AMC38_snATAC, HC, Unstimulated
- GSM9222136 Multiome, AMC38_SARS_snRNA, HC, SARS-CoV-2 in vitro
- GSM9222137 Multiome, AMC38_SARS_snATAC, HC, SARS-CoV-2 in vitro
- GSM9222138 Multiome, AMC12_snRNA, HC, Unstimulated
- GSM9222139 Multiome, AMC12_snATAC, HC, Unstimulated
- GSM9222140 Multiome, AMC12_SARS_snRNA, HC, SARS-CoV-2 in vitro
- GSM9222141 Multiome, AMC12_SARS_snATAC, HC, SARS-CoV-2 in vitro
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