Article ; Online: Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection.
The Journal of infectious diseases
2023 Volume 229, Issue 3, Page(s) 753–762
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Humans ; CD4-Positive T-Lymphocytes ; HIV-1 ; Anti-Retroviral Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; HIV Infections ; Glucose | ||||||||||
| Chemical Substances | Anti-Retroviral Agents ; Glucose (IY9XDZ35W2) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2023-10-09 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article | ||||||||||
| ZDB-ID | 3019-3 | ||||||||||
| ISSN | 1537-6613 ; 0022-1899 | ||||||||||
| ISSN (online) | 1537-6613 | ||||||||||
| ISSN | 0022-1899 | ||||||||||
| DOI | 10.1093/infdis/jiad432 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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