Abstract
BackgroundCytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the general population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. The study explores the effect of latent CMV infection on T-cell subsets, monocyte/macrophages activation markers, and CRP in PLWH on long-term ART.MethodsCross-sectional cohort study including PLWH on long-term suppressive ART. Individuals of 4 groups (HIV+CMV−, HIV+CMV+, HIV−CMV+, and HIV−CMV−) were matched 1:1:1:1 for age and sex. Immunophenotyping of lymphocyte and T-cell subsets by multicolor flow cytometry was performed in fresh blood samples collected from patients and healthy donors.ResultsBoth, latent CMV and treated HIV infection were associated with an expansion of CD8 T cells, a reduced CD4/CD8 ratio, and with CD8 T-cell activation with a cumulative effect in CMV/HIV-coinfected individuals. CMV was associated with elevated numbers of late effector and terminally differentiated CD8 T-cells. Compared to CMV monoinfection, CMV/HIV coinfection showed to be associated with lower proportion of CD28−CD8+ T cells expressing CD57 suggesting that HIV preferentially expands CD28−CD57−CD8+ T cells and impedes terminal differentiation of CD28−CD8+ T cells. We could not show any association between HIV or CMV infection status and concentration of CRP and CD163.ConclusionsCMV infection is associated with phenotypic signs of T-cell senescence, promoting exacerbation and persistence of alterations of the T-cell compartment in PLWH on effective ART, which are associated with adverse clinical outcomes and may be an attractive target for therapeutic interventions.
Highlights
Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the gen‐ eral population, whereas its differential impact in people living with HIV (PLWH) is less well characterized
Effect of infection with HIV and/or CMV on lymphocyte subsets, T‐cell activation and T‐cell subpopulations In our four cohorts matched for sex and age, we found that treated HIV monoinfection and isolated CMV infection are associated with similar levels of activation of CD8 T cells with a cumulative effect in PLWH with long term Antiretroviral therapy (ART) and CMV coinfection resulting in high numbers of activated CD8 T cells
In concordance to the results of the study of Lee and colleagues restricted to patients with confirmed latent CMV infection, we show that treated HIV infection compared to CMV-monoinfection is associated with lower proportion of CD28−CD8+ T cells expressing CD57 [15]
Summary
Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the gen‐ eral population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. Markers of inflammation like c-reactive protein (CRP) and of monocyte/macrophage activation, like soluble CD14 (sCD14) and soluble CD163 (sCD163), have been shown to be elevated in HIV infection and to be associated with the risk for non-AIDS-defining morbidity, especially with cardiovascular disease [5,6,7,8,9,10,11]. In PLWH, ART improves many of these HIV-induced immunologic alterations, but the effect is incomplete, and markers of immune activation, inflammation and T-cell differentiation remain altered. Chronic coinfection with CMV has been identified to strongly contribute to persistent immune activation, to be associated with lower CD4/ CD8 T-cell ratios, with reduced expression of CD28 and increased expression of CD57 in PLWH people with HIV on long term ART [3, 12,13,14]
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