Phenotype and Polyfunctional Deregulation Involving Interleukin 6 (IL-6)– and IL-10–Producing Monocytes in HIV-Infected Patients Receiving Combination Antiretroviral Therapy Differ From Those in Healthy Older Individuals

Pablo-Bernal, Rebeca S. de; Ramos, Rubén; Genebat, Miguel; Cañizares, Julio; Benhnia, Mohammed Rafii‐El‐Idrissi; Muñoz‐Fernández, María Ángeles; Pacheco, Yolanda M.; Galvá, M. I.; Leal, Manuel; Ruiz‐Mateos, Ezequiel

doi:10.1093/infdis/jiv520

Cited by 14 publications

(14 citation statements)

References 27 publications

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“…The maintenance of the higher expression levels of CD300a inhibitory receptor in cART-treated HIV-1-infected subjects could be a reflection of the continuous immune activation in these patients, even after cART. It is well known that although cART decreases viral load to undetectable levels, as HIV is not completely eradicated, the activation of the immune system still occurs ( 32 , 42 – 45 ).…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

et al. 2018

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The ability of the CD300a inhibitory receptor to modulate immune cell functions and its involvement in the pathogenesis of many diseases has aroused a great interest in this molecule. Within human CD4+ T lymphocytes from healthy donors, the inhibitory receptor CD300a is differentially expressed among different T helper subsets. However, there are no data about the expression and regulation of CD300a receptor on CD4+ T cells from human immunodeficiency virus (HIV)-1-infected patients. The objective of this study was to investigate the expression of CD300a on CD4+ T cells from HIV-infected patients on suppressive combined antiretroviral therapy (cART) and cART naïve patients. Our results have demonstrated that the expression levels of this inhibitory receptor were higher on CD4+ T cells from HIV-1 infected subjects compared with healthy donors, and that cART did not reverse the altered expression of CD300a receptor in these patients. We have observed an increase of CD300a expression on both PD1+CD4+ and CD38+CD4+ T cells from HIV-1 infected people. Interestingly, a triple positive (CD300a+PD1+CD38+) subset was expanded in naïve HIV-1 infected patients, while it was very rare in healthy donors and patients on cART. Finally, we found a negative correlation of CD300a expression on CD4+ T lymphocytes and some markers associated with HIV-1 disease progression. Thus, our results show that HIV-1 infection has an impact in the regulation of CD300a inhibitory receptor expression levels, and further studies will shed light into the role of this cell surface receptor in the pathogenesis of HIV infection.

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Section: Discussionmentioning

confidence: 99%

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

et al. 2018

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“… 17 One of the main drivers of arterial inflammation is activated monocyte production of interleukin 6 (IL–6). 18 , 19 IL–6 has been strongly associated with atherosclerotic disease 20 – 22 and all–cause mortality among HIV–infected persons in Botswana and elsewhere. 22 , 23 Similarly, soluble CD163, a haemoglobin scavenger protein released from activated monocytes, has been linked to arterial inflammation and all–cause mortality among HIV–infected persons.…”

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confidence: 99%

HIV disease is associated with increased biomarkers of endothelial dysfunction despite viral suppression on long-term antiretroviral therapy in Botswana

Mosepele

Mohammed

Mupfumi

et al. 2018

CVJA

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SummaryBackgroundUntreated HIV infection is associated with increased biomarkers of endothelial dysfunction. However, the predictors and degree of endothelial dysfunction among virally suppressed HIV–infected adults on long–term antiretroviral therapy (ART) have not been well studied in sub– Saharan Africa (SSA). MethodsWe enrolled 112 HIV–infected adults with virological suppression on long–term ART and 84 HIV–uninfected controls in Botswana. We measured plasma levels of markers of endothelial injury [soluble vascular adhesion molecule 1 (VCAM–1), intercellular adhesion molecule 1 (ICAM–1) and E–selectin] and plasma levels of biomarkers of inflammation [interleukin 6 (IL–6)] and monocyte activation (sCD163). Baseline traditional cardiovascular disease (CVD) risk factors and bilateral common carotid intima–media thickness (cIMT) were also available for all participants. We assessed whether HIV status (despite virological suppression on ART) was associated with biomarkers of endothelial dysfunction after controlling for traditional CVD risk factors in linear regression models. We additionally assessed the association between IL–6, sCD163 and cIMT with endothelial dysfunction in separate multivariate linear regression models, controlling for cIMT, among virally suppressed HIV–infected participants only.ResultsIn multivariate analysis, HIV infection was significantly associated with increased VCAM–1 (p < 0.01) and ICAM–1 (p = 0.03) but not E–selectin (p = 0.74) levels. Within the HIV–positive group, higher sCD163 levels were associated with decreased ICAM–1 and E–selectin (p < 0.01 and p = 0.01, respectively) but not VCAM–1 (p = 0.13) levels. IL–6 was not associated with any of the biomarkers of endothelial dysfunction.ConclusionHIV disease was associated with biomarkers of endothelial dysfunction among virally suppressed adults in Botswana on long–term ART after controlling for traditional CVD risk factors. Future work should explore the clinical impact of persistent endothelial dysfunction following longterm HIV viral suppression on the risk of CVD clinical endpoints among HIV–infected patients in this setting.

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“…We observed a high variability on the time of exposure to the MVC-cART previous to vaccination (median [IQR], 16 [5–38] months). Thus, we explored if this could have affected its impact on immunological variables.…”

Section: Resultsmentioning

confidence: 99%

“…It is reasonable to speculate that the added age-associated immunodeficiency could limit or mask the potential benefits of such antiretroviral therapy on the immunological profile. Accordingly, the immunosenescence, which compromises HBV vaccine responsiveness [14], is accentuated or presents unique features in an HIV-infection scenario [37, 38]. On the other hand, it is well-known that age limits HBV vaccine responsiveness [39].…”

Section: Discussionmentioning

confidence: 99%

Improved CD4 T-cell profile and inflammatory levels in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination

Herrero-Fernández

Rosado‐Sánchez

Genebat

et al. 2018

Preprint

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1 on maraviroc-containing therapy is associated with better responsiveness to HBV 2 vaccination. Abstract word count: 250 15 Number of inserts: 5 (3 tables and 2 figures) 16 Number of references: 42 17 ABSTRACT 26Introduction: We previously found that a maraviroc-containing combined 27 antiretroviral therapy (MVC-cART) was associated with a better response to the 28 Hepatitis B Virus (HBV) vaccine in HIV-infected subjects younger than 50 years old. 29 We aimed here to extend our previous analysis including immunological parameters 30 related to inflammation, T-cell and dendritic cell (DC) subsets phenotype and to explore 31 the impact of MVC-cART on these parameters. 32 Methods: We analyzed baseline samples of vaccinated subjects under 50 years old 33 (n=41). We characterized CD4 T-cells according to the distribution of their maturational 34 subsets and the expression of activation, senescence and prone-to-apoptosis markers; we 35 also quantified Treg-cells and main DC subsets. Linear regressions were performed to 36 determine the impact of these variables on the magnitude of vaccine response. Binary 37 logistic regressions were explored to analyze the impact of MVC-cART on 38 immunological parameters. Correlations with the time of MVC exposure were also 39 explored. 40 Results: MVC-cART remained independently associated with HBV-vaccine 41 responsiveness even after adjusting by immunological variables. The 42 %CD4 + CD25 hi FoxP3 + ki67 + and %pDCs were also independently associated. Moreover, 43 HIV-infected subjects on MVC-containing therapy prior to vaccination showed lower 44 inflammatory levels, activated CD4 T-cells and frequency of Treg cells and higher 45 frequency of recent thymic emigrants.46 Conclusion: Treg-cell levels negatively impacted the HBV-vaccine response, whereas 47 higher pDCs levels and a MVC-cART prior to vaccination were associated with better 48 responsiveness. These factors together with the improved phenotypic CD4 T-cell profile 49 and the lower inflammatory levels found in subjects with a MVC-cART prior HBV 50 vaccination could contribute to their enhanced vaccine response. 51 52 Human Inmunodeficiency Virus (HIV)-infected subjects are at high risk for Hepatitis B 53 Virus (HBV) infection and progression of severe, life-threatening hepatic 54 complications, as cirrhosis and hepatocellular carcinoma [1, 2]. To prevent the 55 associated morbimortality, worldwide current guidelines recommend vaccination 56 against HBV in all HIV-infected subjects susceptible to be coinfected by HBV, but the 57 response rates are lower than in HIV non-infected subjects [reviewed in 3]. 58 The best known predictors of vaccine efficacy are undetectable viral load and CD4 T-59 cell counts above 350 cells/mm 3 [3]. Thus, it is well assumed that a successful combined 60 antiretroviral therapy (cART) favors the vaccine response, however, the influence of the 61 type of antiretroviral treatment has been scarcely explored until now. In this line, it was 62 first described that maraviroc (MVC), a CCR5 antagoni...

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Phenotype and Polyfunctional Deregulation Involving Interleukin 6 (IL-6)– and IL-10–Producing Monocytes in HIV-Infected Patients Receiving Combination Antiretroviral Therapy Differ From Those in Healthy Older Individuals

Cited by 14 publications

References 27 publications

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

HIV disease is associated with increased biomarkers of endothelial dysfunction despite viral suppression on long-term antiretroviral therapy in Botswana

Improved CD4 T-cell profile and inflammatory levels in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination

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