TY - JOUR
T1 - Impact of rosuvastatin on the memory potential and functionality of CD8 + T cells from people with HIV.
AU - Perdomo-Celis, Federico
AU - Passaes, Caroline
AU - Monceaux, Valérie
AU - Lambotte, Olivier
AU - Costagliola, Dominique
AU - Chevalier, Mathieu F
AU - Weiss, Laurence
AU - Sáez-Cirión, Asier
N1 - Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2025/4
Y1 - 2025/4
N2 - BACKGROUND: Virus-specific CD8 + T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8 + T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8 + T cells from people on antiretroviral treatment. METHODS: We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8 + T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8 + T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons. FINDINGS: Total and HIV-specific CD8 + T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ + TNF-α + cells. The superior CD8 + T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8 + T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment. INTERPRETATION: CD8 + T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections. FUNDING: The CESAR trial was sponsored by IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).
AB - BACKGROUND: Virus-specific CD8 + T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8 + T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8 + T cells from people on antiretroviral treatment. METHODS: We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8 + T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8 + T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons. FINDINGS: Total and HIV-specific CD8 + T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ + TNF-α + cells. The superior CD8 + T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8 + T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment. INTERPRETATION: CD8 + T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections. FUNDING: The CESAR trial was sponsored by IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).
KW - HIV-1
KW - CD8T cells
KW - Statins
KW - HIV control
KW - HIV remission
KW - T cell reprogramming
UR - https://www.scopus.com/pages/publications/105001366976
U2 - 10.1016/j.ebiom.2025.105672
DO - 10.1016/j.ebiom.2025.105672
M3 - Article
C2 - 40158388
SN - 2352-3964
VL - 114
SP - 1
EP - 13
JO - eBioMedicine
JF - eBioMedicine
M1 - 105672
ER -
