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

Michael A. Eller*, Ting Hong, Matthew Creegan, Martin E. Nau, Eric Sanders-Buell, Bonnie M. Slike, Shelly J. Krebs, Silvia Ratto-Kim, M. Juliana McElrath, Elly T. Katabira, Diane L. Bolton, Nelson L. Michael, Merlin L. Robb, Sodsai Tovanabutra, Jared M. Baeten, Johan K. Sandberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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, 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.

Original languageEnglish
Pages (from-to)197-202
Number of pages6
Issue number2
StatePublished - 1 Feb 2020
Externally publishedYes


  • CD38
  • CD4 T cells
  • HIV-1
  • HLA-DR
  • PD-1
  • antiretroviral therapy
  • immune activation
  • immune reconstitution


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