The Journal of infection · 2026
Early antiretroviral therapy shapes the immunometabolic landscape without reducing the intact HIV reservoir.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Suanzes Paula, Grau-Expósito Judith, Navarro Jordi, Chafino Silvia, Rull Anna, Rando-Segura Ariadna, Álvarez-López Patricia, Descalzo Vicente, García Jorge N, Monforte Arnau, Curran Adrian, Burgos Joaquín, Planas Bibiana, Sanchiz Marta, Genescà Meritxell, Falcó Vicenç, Buzón María José
Аннотация
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.
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.