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Reevaluation of immune activation in the era of cART and an aging HIV-infected population
Lesley R. de Armas, … , Kristopher L. Arheart, Savita Pahwa
Lesley R. de Armas, … , Kristopher L. Arheart, Savita Pahwa
Published October 19, 2017
Citation Information: JCI Insight. 2017;2(20):e95726. https://doi.org/10.1172/jci.insight.95726.
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Research Article AIDS/HIV Aging

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

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Abstract

Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy.

Authors

Lesley R. de Armas, Suresh Pallikkuth, Varghese George, Stefano Rinaldi, Rajendra Pahwa, Kristopher L. Arheart, Savita Pahwa

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Figure 4

Coexpression of immune activation markers on CD4+ T cells at higher frequencies in HIV+ individuals compared with HIV negative (HC) regardless of age.

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Coexpression of immune activation markers on CD4+ T cells at higher freq...
(A) The relationship between frequencies of CD38+HLA-DR+ CD4+ T cells (left) and CD8+ T cells (right) with age (years) is shown. P values indicate results of 2-tailed Student’s t test to measure statistical differences between HIV+ and HC. (B) Ring graphs represent combination gate (Boolean) analysis using the 5 immune activation markers (CD38, HLA-DR, PD-1, ICOS, Ki-67) on CD4+ T cells. Each ring shows relative frequency of cells expressing 0, 1, 2, 3, 4, or 5 markers simultaneously for each group. Multiple t tests were performed to compare relative frequencies from one ring (i.e., study group) to another. *Indicates significant FDR < 1% when compared with HIV+ group. #Indicates significant FDR < 1% when compared with HIV young group.

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