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Youth Who Control HIV on Antiretroviral Therapy Display Unique Plasma Biomarkers and Cellular Transcriptome Profiles
Samiksha A Borkar1, Li Yin1, Guglielmo M Venturi2
1Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA.
Cells
|February 25, 2025
Summary
Early combination antiretroviral therapy (ART) in youth with HIV (YWH) establishes unique biological profiles, mitigating inflammation and potentially preventing viral breakthrough. This research identifies key biomarkers and gene expression patterns for sustained HIV control.
Area of Science:
- Immunology and Virology
- Genomics and Proteomics
- Biomarker Discovery
Background:
- Combination antiretroviral therapy (ART) suppresses HIV-1 replication but does not eliminate latent reservoirs, leading to persistent immune activation and comorbidities.
- Youth with HIV (YWH) initiating ART early, before CD4 T cell decline, offer a unique model to study viral control markers and predictors of viral breakthrough.
- Understanding the biological differences between virally suppressed and non-suppressed YWH is crucial for optimizing HIV treatment strategies.
Purpose of the Study:
- To identify plasma biomarkers and cellular gene expression profiles associated with sustained viral control in youth with HIV (YWH) on early ART.
- To compare multi-omics data between virally suppressed (VS) YWH, non-suppressed (VNS) YWH, and youth with no infection (NI).
- To uncover potential therapeutic targets for limiting viral persistence and improving long-term HIV management.
Main Methods:
- A multi-omics approach was utilized, analyzing plasma biomarkers and cellular gene expression.
- Study participants included 52 individuals: 27 YWH on ART for 144 weeks (19 VS, 8 VNS) and 25 age-matched youth with no infection (NI).
- Virally suppressed status was defined as <50 RNA copies/mL.
Main Results:
- Virally suppressed YWH exhibited distinct multi-omics bioprofiles compared to both VNS YWH and NI individuals.
- Early viral suppression on ART was associated with mitigated inflammatory pathways and normalized biomarkers linked to HIV-related comorbidities.
- Upregulated genes in YWH were associated with cellular homeostasis pathways, including DNA repair, RNA processing, and transcription regulation, potentially contributing to sustained HIV control.
Conclusions:
- Early ART initiation in YWH leads to unique biological profiles that correlate with sustained viral suppression and reduced comorbidity markers.
- Specific gene expression patterns related to cellular homeostasis may play a role in preventing viral breakthrough and maintaining long-term HIV control.
- The identified candidate markers and molecular mechanisms provide potential targets for novel therapeutic strategies aimed at enhancing HIV treatment outcomes.
Keywords:
DNA repairbiomarkersbioprofilescellular homeostasiscomorbiditiesinflammationtranscriptomeviral suppressionyouth with HIVMore Related Videos
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