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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.

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


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.

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