Abstract
Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with Candida albicans and Mycobacterium tuberculosis. In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.
Highlights
Combination antiretroviral therapy has drastically curtailed morbidity and mortality in people living with HIV (PLHIV) [1]
We focused on a set of 108 manually annotated white blood cell (WBC) subsets based on the original 500FG study [19], with the addition of a fifth panel in which we classified monocytes, CD4+ memory and regulatory T cells, and CD8+ cells according to their expression of the CXCR3, CCR4, and CCR6
In this study we show that, despite suppressive Combination antiretroviral therapy (cART), the circulating innate and adaptive immune cell composition in PLHIV differs from that of HIV-uninfected individuals
Summary
Combination antiretroviral therapy (cART) has drastically curtailed morbidity and mortality in people living with HIV (PLHIV) [1]. HIV infection predisposes to non-infectious comorbidities, such as cardiovascular disease and non-AIDSrelated cancer, which share an underlying pathophysiological pathway characterized by a persisting and inappropriate activation of innate and adaptive immune cells [7, 8]. Together, these observations point towards a disbalance in the homeostasis of the immune system, characterized by immunodeficiency on the one hand, and chronic inflammation on the other hand. Heterogeneity in study populations, limited sample sizes of study populations and differences in lifestyle factors, including use of tobacco and recreational drugs, may underlie these inconsistencies and emphasize the need for an integrative approach in evaluating the immune system in PLHIV on stable cART
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