Youth Who Control HIV on Antiretroviral Therapy Display Unique Plasma Biomarkers and Cellular Transcriptome Profiles Including DNA Repair and RNA Processing
Combination antiretroviral therapy (ART) suppresses detectible HIV-1 replication, but latent reservoirs and persistent immune activation contribute to residual viral-associated morbidities and potential viral reactivation. youth with HIV (YWH) virally suppressed on ART early in infection before CD4 T cell decline with fewer comorbidities compared to adults represent a critical population for identifying markers associated with viral control and predictors of viral breakthrough. This study employed a multi-omics approach to evaluate plasma biomarkers and cellular gene expression profiles in 52 participants, including 27 YWH on ART for 144 weeks and 25 youth with no infection (NI) (ages 18-24). Among the 27 YWH, 19 were virally suppressed (VS; <50 RNA copies/mL), while eight were non-suppressed (VNS; >50 RNA copies/mL). VS YWH displayed unique bioprofiles distinct from either VNS or NI. Early viral suppression mitigates inflammatory pathways and normalizes key biomarkers associated with HIV-related comorbidities. Genes upregulated in pathways linked to cellular homeostasis such as DNA repair, RNA processing, and transcription regulation may diminish viral breakthrough and maintain sustained HIV control on ART. Candidate markers and putative molecular mechanisms were identified, offering potential therapeutic targets to limit viral persistence, enhance HIV treatment strategies, and pave the way for improved clinical outcomes.
Authors
- Maureen M. Goodenow (ORCID: https://orcid.org/0000-0002-4750-9627)
- Guglielmo M. Venturi
- Samiksha A. Borkar (ORCID: https://orcid.org/0000-0002-6290-1088)
- Kai-Fen Chang (ORCID: https://orcid.org/0000-0003-3893-7176)
- John W. Sleasman (ORCID: https://orcid.org/0000-0003-0078-5867)
- Jerry Shen (ORCID: https://orcid.org/0000-0003-3293-2307)
- Isaac Raplee (ORCID: https://orcid.org/0000-0002-3105-1287)
- Upasana Nepal
- Li Yin (ORCID: https://orcid.org/0000-0002-3317-4133)
- Bernard M. Fischer (ORCID: https://orcid.org/0000-0001-8066-0516)
Institutions
- National Institutes of Health (US)
- Duke University (US)
- Université Bourgogne Franche-Comté (FR)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Cells
- Published
- 2025-02-15
- DOI
- https://doi.org/10.3390/cells14040285
- Citations
- 3
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.11
Funders
- U.S. Department of Health and Human Services
- University of Southern California
- Children's Hospital of Philadelphia
- University of Miami
- University of Pennsylvania
- University of Florida
- Tulane University
- Johns Hopkins University
- Deutsches Krebsforschungszentrum
- University of South Florida
- Children's National Hospital
- International Maternal Pediatric Adolescent AIDS Clinical Trials Network
- Adolescent Medicine Trials Network for HIV/AIDS Interventions
- Children's Hospital of Michigan
- National Institutes of Health
- Center for AIDS Research, Duke University
- Center for AIDS Research, University of Washington
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Allergy and Infectious Diseases
- National Institute of Child Health and Human Development
- National Center for Research Resources
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- University of Colorado School of Medicine, Anschutz Medical Campus