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PLoS One. 2017 Aug 14;12(8):e0183357. doi: 10.1371/journal.pone.0183357. eCollection 2017.

Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls.

Author information

1
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
2
Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
3
Department of Global Health & Division of Infectious Disease, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
4
HIV Monitoring Foundation, Amsterdam, The Netherlands.
5
Department of Infection and Population Health, University College London, London, United Kingdom.
6
Public health service, Amsterdam, The Netherlands.
7
Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum Universita di Bologna, Bologna, Italy.
8
Department of Medicine, University of California, San Francisco, California, United States of America.
9
Imperial College of Science, Technology and Medicine, London, United Kingdom.

Abstract

HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank. Despite long-term ART (median of 12.2 years), HIV-infected adults had lower CD4+ T-cell counts and higher CD8+ T-cell counts compared to well-matched HIV-negative COBRA participants. The proportion of CD38+HLA-DR+ and PD-1+ CD4+ T-cells was higher in HIV-positive cohort compared to the two HIV-negative cohorts. The proportion CD57+ and CD27-CD28- cells of both CD4+ and CD8+ T-cells in HIV-positives was higher compared to unselected adults (blood bank) as reported before but this difference was not apparent in comparison with well-matched HIV-negative COBRA participants. Multiple regression analysis showed that the presence of an increased proportion of terminally differentiated T cells was strongly associated with CMV infection. Compared to appropriately selected HIV-negative controls, HIV-positive individuals on ART with long-term suppressed viraemia exhibited incomplete immune recovery and increased immune activation/exhaustion. CMV infection rather than treated HIV infection appears to have more consistent effects on measures of terminal differentiation of T cells.

PMID:
28806406
PMCID:
PMC5555623
DOI:
10.1371/journal.pone.0183357
[Indexed for MEDLINE]
Free PMC Article

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