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.
Highlights
Antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection has dramatically reduced AIDS-associated morbidity and mortality [1,2,3]
In the sub-group of participants who were CMV seropositive, we considered the association of each immunological marker with group and i) CMV total IgG and ii) CMV high avidity IgG, with the same adjustments
HIVpositive individuals had been diagnosed with HIV for a mean of 13.9 (4.8) years ago, had been on ART for a mean of 12.2 (4.7) years and had spent a median (IQR) of 8.0 (5.3–10.9) years with an undetectable plasma viral load (Table 1)
Summary
Antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection has dramatically reduced AIDS-associated morbidity and mortality [1,2,3]. Immunological alterations observed during treated HIV-1 infection reflect those observed in the general population during aging [7, 10,11,12] These include high levels of soluble inflammatory and coagulation related proteins, high levels of T cell activation, high levels of T cell exhaustion, low levels of naïve T cells and an extensive proliferative history of CD8 T cells [13,14,15,16,17,18]. These age-associated immunological alterations are referred to as immune senescence [19, 20], the precise definition and clinical significance of this syndrome remains controversial [4, 21, 22]
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