Early antiretroviral therapy shapes the immunometabolic landscape without reducing the intact HIV reservoir
Suanzes, Paula (Universitat Autònoma de Barcelona. Departament de Medicina)
Grau Expósito, Judith (Vall d'Hebron Institut de Recerca (VHIR))
Navarro, Jordi (Vall d'Hebron Institut de Recerca (VHIR))
Chafino, Silvia (Hospital Universitari Joan XXIII de Tarragona)
Rull, Anna (Hospital Universitari Joan XXIII de Tarragona)
Rando-Segura, Ariadna (Hospital Universitari Vall d'Hebron)
Álvarez-López, Patricia (Vall d'Hebron Institut de Recerca (VHIR))
Descalzo Jorro, Vicente (Vall d'Hebron Institut de Recerca (VHIR))
García Pérez, Jorge Néstor (Vall d'Hebron Institut de Recerca (VHIR))
Monforte-Pallarés, Arnau (Universitat Autònoma de Barcelona. Departament de Medicina)
Curran, Adrian (Vall d'Hebron Institut de Recerca (VHIR))
Burgos, Joaquín (Universitat Autònoma de Barcelona. Departament de Medicina)
Planas, Bibiana (Vall d'Hebron Institut de Recerca (VHIR))
Sanchiz Cruz, Marta (Vall d'Hebron Institut de Recerca (VHIR))
Genescà Ferrer, Meritxell (Vall d'Hebron Institut de Recerca (VHIR))
Falcó, Vicenç (Universitat Autònoma de Barcelona. Departament de Medicina)
Buzón, Maria José (Vall d'Hebron Institut de Recerca (VHIR))

Data:	2026
Resum:	Objectives: We assessed the effect of early ART during acute HIV infection on reservoir dynamics, cytokine profile, and T-cell metabolism. Methods: We studied a longitudinal cohort of PWH starting ART during early (ET) or chronic (CT) infection, and a cross-sectional cohort including matched ET and CT participants (≥36 months virologically suppressed) and HIV-negative controls. We analysed total HIV-DNA, intact and defective proviruses, cell-associated HIV-RNA, plasma cytokines, and metabolomic profiles of CD4+ and CD8+T-cells. Results: Over 75% of ET participants started ART in Fiebig stages IV-VI. Early ART was associated with lower total HIV-DNA and cell-associated RNA. Although intact proviruses were similar between groups, they represented a larger proportion of the reservoir in ET participants. Worse pre-ART immune status correlated with a larger and more transcriptionally active reservoir. Regulatory, inflammatory, and homeostatic cytokines negatively correlated with the intact reservoir, particularly in CT participants. Metabolomic profiling of T-cells demonstrated ART timing-dependent alterations in several metabolic pathways. Metabolites involved in glycolysis, amino-acid metabolism, and polyol pathways positively correlated with HIV transcription in CD4⁺T-cells, especially in CT participants. Conclusion: Early ART limits the HIV reservoir size, shapes its composition, and influences immunometabolic pathways, though it might not be enough to reduce the intact reservoir.
Ajuts:	Instituto de Salud Carlos III PI20/00823 Instituto de Salud Carlos III CPII22/00005
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	HIV ; HIV infections ; HIV reservoir ; Inflammation ; Immunometabolism ; Metabolomics ; Cytokines ; HIV Seroconversion
Publicat a:	Journal of Infection, April 2026, art. 106754, ISSN 1532-2742

DOI: 10.1016/j.jinf.2026.106754

15 p, 8.7 MB

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