biostudies-literatureZhao JBLRD VANIAID NIH HHSU.S. Department of DefenseDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesNIH HHSCenter for Integrated Healthcare, U.S. Department of Veterans Affairs658420https://www.ebi.ac.uk/biostudies/studies/S-EPMC8129510biostudies-literatureUnknown12The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable rFrontiers in immunologyMitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV.PMC8129510R15 AI143377PR170067S10 OD021572I01 BX002670R01 AI1147481I01BX002670, 1I01BX004281R21 AI138598R21AI138598, R01AI114748, S10OD021572I01 BX004281Nguyen LNTMorrison ZDMoorman JPZhang JLu ZCao DKhanal SThakuri BKCWang LOgbu SCLiu YGazzar MENing SLi ZNguyen LNYao ZQWu XYZhao JDang XSchank MfalseMitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV.The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable r2021-01-01T00:00:00Z20212025-04-18T21:55:18.937Z2025-04-07T09:41:14.837ZS-EPMC81295103401733510.3389/fimmu.2021.658420