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Article

Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size

by
Erick De La Torre Tarazona
1,2,*,
Elisa Moraga
3,
María Fons-Contreras
1,
Raúl Vaquer
1,
Sonsoles Sánchez-Palomino
2,3,
Germán Vallejo-Palma
4,
Sergio Calderón-Vicente
1,5,
Sònia Vicens-Artés
3,
Teresa Aldamiz-Echevarria
2,6,
Marianela Ciudad Sañudo
7,
Cristina Moreno
2,8,
Inés Armenteros-Yeguas
9,
Juan Tiraboschi
10,
Sergio Reus Bañuls
11,
José Alcamí
3,
Sergio Serrano-Villar
1,2 and
Santiago Moreno
1,2,12,*,† on behalf of the CoRIS cohort
1
Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
2
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
3
HIV Unit, Infectious Diseases Service, Hospital Clinic, IDIBAPS, AIDS and HIV Research Group, University of Barcelona, 08036 Barcelona, Spain
4
General Pediatrics and Infectious and Tropical Diseases Department, Hospital La Paz, 28046 Madrid, Spain
5
Department of Biochemistry and Molecular Biology, Complutense de Madrid University, 28040 Madrid, Spain
6
Clinical Microbiology and Infectious Diseases Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
7
Hospital Universitario de La Princesa, 28006 Madrid, Spain
8
Centro Nacional de Epidemiología, Instituto de Salud Carlos III, 28029 Madrid, Spain
9
Centro Sanitario Sandoval, Hospital Universitario Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, 28010 Madrid, Spain
10
HIV Unit and Infectious Diseases Service, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain
11
Infectious Diseases Unit, Hospital General Universitario Dr. Balmis de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, 03010 Alicante, Spain
12
Department of Medicine, Alcalá University, 28871 Madrid, Spain
 
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*
Authors to whom correspondence should be addressed.
†
Membership of the Team Name is provided in the Appendix A.
Int. J. Mol. Sci. 2025, 26(17), 8430; https://doi.org/10.3390/ijms26178430
Submission received: 15 July 2025 / Revised: 22 August 2025 / Accepted: 27 August 2025 / Published: 29 August 2025
(This article belongs to the Special Issue Advances in Immunology and Inflammation During and After Infectious Diseases)
Review Reports Versions Notes

Abstract

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.
Keywords: HIV reservoir; intact proviruses; inflammatory markers; stem cell factor HIV reservoir; intact proviruses; inflammatory markers; stem cell factor

Share and Cite

MDPI and ACS Style

De La Torre Tarazona, E.; Moraga, E.; Fons-Contreras, M.; Vaquer, R.; Sánchez-Palomino, S.; Vallejo-Palma, G.; Calderón-Vicente, S.; Vicens-Artés, S.; Aldamiz-Echevarria, T.; Sañudo, M.C.; et al. Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size. Int. J. Mol. Sci. 2025, 26, 8430. https://doi.org/10.3390/ijms26178430

AMA Style

De La Torre Tarazona E, Moraga E, Fons-Contreras M, Vaquer R, Sánchez-Palomino S, Vallejo-Palma G, Calderón-Vicente S, Vicens-Artés S, Aldamiz-Echevarria T, Sañudo MC, et al. Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size. International Journal of Molecular Sciences. 2025; 26(17):8430. https://doi.org/10.3390/ijms26178430

Chicago/Turabian Style

De La Torre Tarazona, Erick, Elisa Moraga, María Fons-Contreras, Raúl Vaquer, Sonsoles Sánchez-Palomino, Germán Vallejo-Palma, Sergio Calderón-Vicente, Sònia Vicens-Artés, Teresa Aldamiz-Echevarria, Marianela Ciudad Sañudo, and et al. 2025. "Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size" International Journal of Molecular Sciences 26, no. 17: 8430. https://doi.org/10.3390/ijms26178430

APA Style

De La Torre Tarazona, E., Moraga, E., Fons-Contreras, M., Vaquer, R., Sánchez-Palomino, S., Vallejo-Palma, G., Calderón-Vicente, S., Vicens-Artés, S., Aldamiz-Echevarria, T., Sañudo, M. C., Moreno, C., Armenteros-Yeguas, I., Tiraboschi, J., Reus Bañuls, S., Alcamí, J., Serrano-Villar, S., & Moreno, S., on behalf of the CoRIS cohort. (2025). Identification of Inflammation Markers as Novel Potential Predictors of the HIV-DNA Reservoir Size. International Journal of Molecular Sciences, 26(17), 8430. https://doi.org/10.3390/ijms26178430

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