Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection
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Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection. / Naidoo, Kewreshini K; Highton, Andrew J; Baiyegunhi, Omolara O; Bhengu, Sindiswa P; Dong, Krista L; Bunders, Madeleine J; Altfeld, Marcus; Ndung'u, Thumbi.
in: J INFECT DIS, Jahrgang 229, Nr. 3, 14.03.2024, S. 753-762.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection
AU - Naidoo, Kewreshini K
AU - Highton, Andrew J
AU - Baiyegunhi, Omolara O
AU - Bhengu, Sindiswa P
AU - Dong, Krista L
AU - Bunders, Madeleine J
AU - Altfeld, Marcus
AU - Ndung'u, Thumbi
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024/3/14
Y1 - 2024/3/14
N2 - BACKGROUND: Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1-associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function.METHODS: Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions.RESULTS: Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression.CONCLUSIONS: ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.
AB - BACKGROUND: Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1-associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function.METHODS: Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions.RESULTS: Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression.CONCLUSIONS: ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.
KW - Anti-Retroviral Agents/therapeutic use
KW - CD4-Positive T-Lymphocytes
KW - Glucose
KW - HIV Infections
KW - HIV-1
KW - Humans
U2 - 10.1093/infdis/jiad432
DO - 10.1093/infdis/jiad432
M3 - SCORING: Journal article
C2 - 37804102
VL - 229
SP - 753
EP - 762
JO - J INFECT DIS
JF - J INFECT DIS
SN - 0022-1899
IS - 3
ER -