Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size
The dynamics of the HIV reservoir during antiretroviral therapy (ART) exhibit variability, with a pronounced decline during the initial years of treatment. However, the identification of biomarkers and host factors associated with the decay of the different forms of HIV proviruses remains to be fully elucidated. We conducted a longitudinal study on people with HIV provided by the Spanish National HIV cohort. We assessed the HIV-DNA levels by Intact Proviral DNA Assay, and inflammatory markers using the Proximity Extension Assay, before and after ART initiation. A multivariate linear regression model was employed to identify potential predictive markers. Our results highlight the identification of novel inflammatory markers, such as ADA, DNER, CDCP1, SCF, among others, that varied significantly over ART initiation. In addition, we observed several markers associated with intact HIV-DNA before ART initiation (CD8A, CX3CL1, and ST1A1) or during undetectable viral load post-ART (IL-10). Moreover, up to five markers were able to predict the intact HIV reservoir decay over ART. The strongest predictor was Stem Cell Factor (SCF), where higher baseline levels of this marker were associated with a greater decline in the intact HIV reservoir. In conclusion, we have identified inflammatory markers associated with the size and dynamics of the HIV-DNA reservoir. These findings provide new insights that could contribute to the development of multi-targeted intervention strategies aimed at modulating or monitoring the HIV reservoir size.
Authors
- Marianela Ciudad Sañudo
- Sònia Vicens‐Artés (ORCID: https://orcid.org/0000-0002-3839-0417)
- Elisa Moraga (ORCID: https://orcid.org/0000-0001-5913-364X)
- Juan Tiraboschi (ORCID: https://orcid.org/0000-0002-0073-873X)
- Sergio Reus (ORCID: https://orcid.org/0000-0002-3320-9754)
- Erick De La Torre Tarazona (ORCID: https://orcid.org/0000-0003-0325-3735)
- Inés Armenteros Yeguas (ORCID: https://orcid.org/0009-0006-2435-1368)
- Teresa Aldámiz‐Echevarría (ORCID: https://orcid.org/0000-0002-4374-6940)
- Sergio Serrano‐Villar (ORCID: https://orcid.org/0000-0002-5447-3554)
- José Alcamı́ (ORCID: https://orcid.org/0000-0003-0023-7377)
- Santiago Moreno (ORCID: https://orcid.org/0000-0002-2843-1094)
- Cristina Moreno (ORCID: https://orcid.org/0000-0002-3378-3158)
- Germán Vallejo-Palma (ORCID: https://orcid.org/0009-0001-0770-0355)
- Sonsoles Sánchez-Palomino (ORCID: https://orcid.org/0000-0002-9142-812X)
- María Fons-Contreras
- Raúl Vaquer
- Sergio Calderón-Vicente (ORCID: https://orcid.org/0000-0003-1328-2847)
Institutions
- Universidad Complutense de Madrid (ES)
- Universidad de Alcalá (ES)
- Hospital Universitario La Paz (ES)
- Instituto de Salud Carlos III (ES)
- Bellvitge University Hospital (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Hospital Clínico San Carlos (ES)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES)
- Centro Nacional de Epidemiología (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Clínic de Barcelona (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Hospital Universitario de La Princesa (ES)
- Hospital General Universitario de Alicante Doctor Balmis (ES)
- Hospital Universitario Ramón y Cajal (ES)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-08-29
- DOI
- https://doi.org/10.3390/ijms26178430
- Citations
- 1
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.04
Funders
- European Commission
- Ministerio de Ciencia e Innovación
- Instituto de Salud Carlos III