Early antiretroviral therapy shapes the immunometabolic landscape without reducing the intact HIV reservoir
Journal of Infection, 2026
Suanzes P., Grau-Expósito J., Navarro J., Chafino S., Rull A., Rando-Segura A., Álvarez-López P., Descalzo V., García J., Monforte A., Curran A., Burgos J., Planas B., Sanchiz M., Genescà M., Falcó V., Buzón M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 48 |
Abstract
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.