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

• Published in: PloS one 2017-08, Vol.12 (8), p.e0183357-e0183357
• Main Authors: Booiman, Thijs, Wit, Ferdinand W, Girigorie, Arginell F, Maurer, Irma, De Francesco, Davide, Sabin, Caroline A, Harskamp, Agnes M, Prins, Maria, Franceschi, Claudio, Deeks, Steven G, Winston, Alan, Reiss, Peter, Kootstra, Neeltje A
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; Adults; Age; Aged; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biology and Life Sciences; Blood; Blood banks; Blood Donors; Care and treatment; Case-Control Studies; CD27 antigen; CD28 antigen; CD38 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD57 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Cytomegalovirus; Cytomegalovirus - physiology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Demographics; Differentiation; Dosage and administration; Exhaustion; Health aspects; Histocompatibility antigen HLA; HIV; HIV infections; HIV Seropositivity - drug therapy; HIV Seropositivity - immunology; HIV Seropositivity - virology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Infections; Life Style; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Management; Medicine and Health Sciences; Morbidity; Multiple regression analysis; PD-1 protein; Physiological aspects; Regression analysis; T cell receptors; T cells; Viremia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183357

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.