Activated PD-1+ CD4 T cells represent a short-lived part of the viral reservoir and predict poor immunologic recovery upon initiation of ART.

OBJECTIVE Activated (CD38+HLA-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, 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.