Activated PD-1+ CD4+ T cells represent a short-lived part of the viral reservoir and predict poor immunologic recovery upon initiation of ART
| Autor: | Bonnie M. Slike, Silvia Ratto-Kim, Sodsai Tovanabutra, Johan K. Sandberg, Martin E. Nau, Eric Sanders-Buell, Diane L. Bolton, Jared M. Baeten, Shelly J. Krebs, Merlin L. Robb, Michael A. Eller, M. Juliana McElrath, Matthew Creegan, Nelson L. Michael, Ting Hong, Elly Katabira |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male Immunology Population Programmed Cell Death 1 Receptor Inflammation HIV Infections Baseline level Biology Lymphocyte Activation Virus Replication 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Humans Uganda 030212 general & internal medicine education education.field_of_study Disease progression Plasma levels Viral Load CD4 Lymphocyte Count 030104 developmental biology Infectious Diseases Viral replication Anti-Retroviral Agents Concomitant HIV-1 Linear Models RNA Viral Female medicine.symptom Viral load |
| Zdroj: | AIDS (London, England). 34(2) |
| ISSN: | 1473-5571 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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