OBJECTIVE: Activated (CD38HLA-DR) PD-1 CD4 T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4 T-cell populations to measure relative contributions to viral reservoirs. DESIGN: Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4 T-cell populations and their contribution to viral reservoirs. METHODS: We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4 T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform. RESULTS: Concomitant with viral load decline and CD4 T-cell count rebound, the activated PD-1 CD4 T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1 CD4 T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1 CD4 T cells was associated with poorer CD4 T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover. CONCLUSION: Activated PD-1 CD4 T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.
OBJECTIVE: Activated (CD38HLA-DR) PD-1CD4 T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4 T-cell populations to measure relative contributions to viral reservoirs. DESIGN: Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4 T-cell populations and their contribution to viral reservoirs. METHODS: We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4 T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform. RESULTS: Concomitant with viral load decline and CD4 T-cell count rebound, the activated PD-1CD4 T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1CD4 T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1CD4 T cells was associated with poorer CD4 T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover. CONCLUSION: Activated PD-1CD4 T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.
Authors: Eric G Meissner; Dongjun Chung; Betty Tsao; David W Haas; Netanya S Utay Journal: AIDS Res Hum Retroviruses Date: 2020-11-11 Impact factor: 1.723