RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV‐1‐positive men

Gibellini, Davide; Borderi, Marco; Crignis, Elisa De; Cicola, Ronny; Vescini, Fabio; Caudarella, Renata; Chiodo, Francesco; Re, Maria Carla

doi:10.1002/jmv.20938

Cited by 85 publications

(65 citation statements)

References 50 publications

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“…Limited data from in vivo studies on levels of circulating RANKL 21-23 and OPG 22,23 in untreated and treated HIV-1 infection are conflicting. A recent study found that serum RANKL was lower in HIV-infected individuals than controls and was negatively associated with the number of coronary segments with plaque and Agatston coronary artery calcium score in HIV-1-infected individuals even after adjusting for traditional cardiovascular risk factors.…”

Section: Discussionmentioning

confidence: 94%

Perturbations of Circulating Levels of RANKL-Osteoprotegerin Axis in Relation to Lipids and Progression of Atherosclerosis in HIV-Infected and -Uninfected Adults: ACTG NWCS 332/A5078 Study

Kelesidis

Kendall²,

Yang³

et al. 2013

AIDS Research and Human Retroviruses

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The receptor activator of the NF-κB ligand (RANKL)-osteoprotegerin (OPG) axis has been shown to play a role in the inflammatory process of atherogenesis and may be regulated by changes in levels of cholesterol. However, the interplay between HIV-1 infection, lipids, the RANKL-OPG axis, and atherosclerosis is poorly defined. Serum RANKL, OPG, and RANKL/OPG ratio were retrospectively assessed for 91 subjects from a 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1 uninfected (n=36) or HIV-1(+) with (n=29) or without (n=26) continuous protease inhibitor (PI)-based therapy for ≥2 years. Associations of serum RANKL, OPG, and RANKL/OPG ratio to the primary outcomes of levels of circulating lipids and atherosclerosis progression were determined using multivariate regression models. Serum RANKL and RANKL/OPG ratio were significantly lower in HIV-infected versus HIV-uninfected subjects (p<0.01). Multivariate models for HIV-1(+) subjects, but not in uninfected controls, demonstrated that perturbations in serum cholesterol levels were significantly associated (p<0.05) with perturbations in serum levels of RANKL and OPG, and their ratio (RANKL/OPG). There were no significant associations of serum RANKL, OPG, and RANKL/OPG with progression of atherosclerosis in HIV-1(+) subjects. Our results suggest that HIV-1 infection is associated with reductions in both serum RANKL and the RANKL/OPG ratio, and perturbations in the circulating levels of RANKL and OPG are significantly associated with increases in cholesterol levels, but not with progression of atherosclerosis.

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Section: Discussionmentioning

confidence: 94%

Perturbations of Circulating Levels of RANKL-Osteoprotegerin Axis in Relation to Lipids and Progression of Atherosclerosis in HIV-Infected and -Uninfected Adults: ACTG NWCS 332/A5078 Study

Kelesidis

Kendall²,

Yang³

et al. 2013

AIDS Research and Human Retroviruses

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“…[14][15][16] High concentrations of HIV RNA have been associated with elevated levels of receptor activator of nuclear factor κ β ligand (RANKL), an osteoblast secreted cytokine that promotes osteoclast formation. 17 Osteoporosis was reported in about 10-13% of HIV subjects in western population. 18 In present study osteoporosis was percent in 29.6% of cases which is much higher as compared to study by Bruera et al 18 There could be several reasons.…”

Section: Discussionmentioning

confidence: 99%

A study of bone mineral density among people living with HIV in India and its correlation with CD4 count

et al. 2017

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Background: Data on the prevalence of osteoporosis in HIV patients in Asian population is scarce this study was done to find out the prevalence of osteoporosis in HIV infected patients and its correlation with CD4 counts.Methods: This cross- sectional study was conducted in NACO- ART center of tertiary care hospital. Total 115 HIV patients were included in this study which were divided into ART naive (n= 69) and patients taking ART (n= 46). We analysed BMD by DEXA in 115 HIV positive patients and 78 HIV negative age and sex matched controls. Correlation of BMD with a CD4 count and ART regimen was studied.Results: BMD was found to be low in HIV positive patients. T score in HIV positive patients was significantly lower (p<0.05) as compared to the HIV negative control group. The prevalence of osteopenia and osteoporosis in HIV positive patients was 50.4% and 29.6% respectively, as compared to 23.1% and 2.6% in HIV negative controls. BMD showed relation with CD4 count. We did not find any statistical difference between any ART regimen and BMD.Conclusions: The prevalence of osteopenia and osteoporosis in HIV infected cases was higher as compared to HIV negative controls and higher in ART group as compared to ART naïve group. Low BMD levels show correlation with low CD4 count. We recommend that HIV positive patients especially with advanced stage of disease, low CD4 count should be screened for low BMD by DEXA scan for osteoporosis and managed accordingly

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“…In vitro treatment of primary lymphocytes from suppressed HIV-1-infected individuals with soluble TRAIL showed reductions in viral replication without drastic alterations in cytokine profiles (50). In our studies, we used concentrations of TRAIL that can be found in vivo in viremic HIV-1-infected individuals (46). Thus, the utility of CSF-1R antagonists in HIV-1 infection could be explored in the setting of clinical protocols for treatment of certain myeloproliferative conditions that employ CSF-1R antagonists.…”

Section: Discussionmentioning

confidence: 99%

Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing

Cunyat

Rainho

West³

et al. 2016

J Virol

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Strategies aimed at eliminating persistent viral reservoirs from HIV-1-infected individuals have focused on CD4؉ T-cell reservoirs. However, very little attention has been given to approaches that could promote elimination of tissue macrophage reservoirs. HIV-1 infection of macrophages induces phosphorylation of colony-stimulating factor 1 receptor (CSF-1R), which confers resistance to apoptotic pathways driven by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thereby promoting viral persistence. In this study, we assessed whether CSF-1R antagonists (PLX647, PLX3397, and PLX5622) restored apoptotic sensitivity of HIV-1-infected macrophages in vitro. PLX647, PLX3397, and PLX5622 at clinically relevant concentrations blocked the activation of CSF-1R and reduced the viability of infected macrophages, as well as the extent of viral replication. Our data show that strategies targeting monocyte colony-stimulating factor (MCSF) signaling could be used to promote elimination of HIV-1-infected myeloid cells and to contribute to the elimination of persistent viral reservoirs. IMPORTANCEAs the HIV/AIDS research field explores approaches to eliminate HIV-1 in individuals on suppressive antiviral therapy, those approaches will need to eliminate both CD4 ؉ T-cell and myeloid cell reservoirs. Most of the attention has focused on CD4 ؉ Tcell reservoirs, and scant attention has been paid to myeloid cell reservoirs. The distinct nature of the infection in myeloid cells versus CD4؉ T cells will likely dictate different approaches in order to achieve their elimination. For CD4 ؉ T cells, most strategies focus on promoting virus reactivation to promote immune-mediated clearance and/or elimination by viral cytopathicity. Macrophages resist viral cytopathic effects and CD8؉ T-cell killing. Therefore, we have explored clearance strategies that render macrophages sensitive to viral cytopathicity. This research helps inform the design of strategies to promote clearance of the macrophage reservoir in infected individuals on suppressive antiviral therapy. Macrophages are permissive to infection by primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) (1-3); have a prolonged life span (4, 5); and are widely distributed throughout the body in tissues like the lymph nodes (6), gut (7-9), central nervous system (10), and lung (11). Because macrophages are resistant to viral cytopathic effects, they have the potential to act as a viral reservoir in HIV-1-infected individuals on suppressive antiretroviral therapy (ART) (1, 12-17). Furthermore, infected macrophages harbor infectious HIV-1 particles in stable intracellular virus-containing compartments (VCCs) that are connected to the plasma membrane (18). These VCCs protect the archived virions from antibody-mediated neutralization (19) while enabling infection in trans at virological synapses with nearby T cells (13,20). These synapses promote cell-to-cell transmission and a high multiplicity of infect...

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RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV‐1‐positive men

Cited by 85 publications

References 50 publications

Perturbations of Circulating Levels of RANKL-Osteoprotegerin Axis in Relation to Lipids and Progression of Atherosclerosis in HIV-Infected and -Uninfected Adults: ACTG NWCS 332/A5078 Study

Perturbations of Circulating Levels of RANKL-Osteoprotegerin Axis in Relation to Lipids and Progression of Atherosclerosis in HIV-Infected and -Uninfected Adults: ACTG NWCS 332/A5078 Study

A study of bone mineral density among people living with HIV in India and its correlation with CD4 count

Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing

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