scholarly journals Non-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leila B. Giron ◽  
Clovis S. Palmer ◽  
Qin Liu ◽  
Xiangfan Yin ◽  
Emmanouil Papasavvas ◽  
...  
Keyword(s):  
Treatment Interruption ◽  
Post Treatment ◽  
Machine Learning Algorithms ◽  
Virologic Suppression ◽  
Hiv Latency ◽  
Viral Rebound ◽  
Treatment Control ◽  
Non Invasive ◽  
Metabolic Biomarkers

AbstractNon-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the host pathways involved in post-ART HIV control. Here we report plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-remission using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. These signatures remain significant after adjusting for key demographic and clinical confounders. We also report mechanistic links between some of these biomarkers and HIV latency reactivation and/or myeloid inflammation in vitro. Finally, machine learning algorithms, based on selected sets of these biomarkers, predict time-to-viral-rebound with 74% capacity and probability-of-viral-remission with 97.5% capacity. In summary, we report non-invasive plasma biomarkers, with potential functional significance, that predict both the duration and probability of HIV remission after treatment interruption.

scholarly journals Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

2021 ◽  
Author(s):  
Leila Giron ◽  
Clovis Palmer ◽  
Qin Liu ◽  
Xiangfan Yin ◽  
Emmanouil Papasavvas ◽  
...  
Keyword(s):  
Treatment Interruption ◽  
Post Treatment ◽  
Machine Learning Algorithms ◽  
Virologic Suppression ◽  
Viral Rebound ◽  
Hiv Cure ◽  
Non Invasive ◽  
Metabolic Biomarkers ◽  
Hiv Cure Research

Abstract Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74-76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

scholarly journals Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

2020 ◽  
Author(s):  
Leila Giron ◽  
Clovis Palmer ◽  
Qin Liu ◽  
Xiangfan Yin ◽  
Emmanouil Papasavvas ◽  
...  
Keyword(s):  
Treatment Interruption ◽  
Post Treatment ◽  
Machine Learning Algorithms ◽  
Virologic Suppression ◽  
Viral Rebound ◽  
Hiv Cure ◽  
Non Invasive ◽  
Metabolic Biomarkers ◽  
Hiv Cure Research

Abstract Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74–76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

scholarly journals Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

2020 ◽  
Author(s):  
Leila B. Giron ◽  
Clovis S. Palmer ◽  
Qin Liu ◽  
Xiangfan Yin ◽  
Emmanouil Papasavvas ◽  
...  
Keyword(s):  
Treatment Interruption ◽  
Post Treatment ◽  
Machine Learning Algorithms ◽  
Virologic Suppression ◽  
Viral Rebound ◽  
Hiv Cure ◽  
Non Invasive ◽  
Metabolic Biomarkers ◽  
Hiv Cure Research

ABSTRACTNon-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74-76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

scholarly journals 4 Post-treatment control or treated controllers? The impact of ART on time to viral rebound in recent seroconverters

2016 ◽  
Vol 2 ◽  
pp. 9
Author(s):  
G.E. Martin ◽  
M. Gossez ◽  
J.P. Williams ◽  
W. Stöhr ◽  
J. Meyerowitz ◽  
...  
Keyword(s):  
Post Treatment ◽  
Viral Rebound ◽  
Treatment Control ◽  
The Impact

scholarly journals Phospholipid Metabolism Is Associated with HIV Rebound Upon Treatment Interruption

2020 ◽  
Author(s):  
Leila B. Giron ◽  
Emmanouil Papasavvas ◽  
Xiangfan Yin ◽  
Aaron R. Goldman ◽  
Hsin-Yao Tang ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Tumor Cells ◽  
Treatment Interruption ◽  
Phospholipid Metabolism ◽  
Biologically Active ◽  
Inflammatory Factors ◽  
Hiv Latency ◽  
Potential Contribution ◽  
Viral Rebound

ABSTRACTLipids are biologically active molecules involved in a variety of cellular processes and immunological functions, including inflammation. It was recently shown that phospholipids and their derivatives, lysophospholipids, can reactivate latent (dormant) tumor cells, causing cancer recurrence. However, the potential link between lipids and HIV latency, persistence, and viral rebound after cessation of antiretroviral therapy (ART) has never been investigated. We explored the links between plasma lipids and the burden of HIV during ART. We profiled the circulating lipidome from the plasma of 24 chronically HIV-infected individuals on suppressive ART who subsequently underwent an analytic treatment interruption (ATI) without concurrent immunotherapies. The pre-ATI viral burden was estimated as time-to-viral-rebound and viral load setpoints post-ATI. We found that higher pre-ATI levels of lysophospholipids, including the pro-inflammatory lysophosphatidylcholine, were associated with faster time-to-viral-rebound and higher viral setpoints upon ART cessation. Furthermore, higher pre-ATI levels of the pro-inflammatory byproduct of intestinal lysophosphatidylcholine metabolism, trimethylamine-N-oxide (TMAO), were also linked to faster viral rebound post-ART. Finally, pre-ATI levels of several phosphatidylcholine species (lysophosphatidylcholine precursors) correlated strongly with higher pre-ATI levels of HIV DNA in peripheral CD4+ T cells. Our proof-of-concept data point to phospholipids and lysophospholipids as plausible pro-inflammatory contributors to HIV persistence and rapid post-ART HIV rebound. The potential interplay between phospholipid metabolism and both the establishment and maintenance of HIV latent reservoirs during- and post-ART warrants further investigation.IMPORTANCEThe likelihood of HIV rebound after stopping antiretroviral therapy (ART) is a function of the interplay between the size of HIV reservoirs that persist despite ART and the host immunological and inflammatory factors that modulate these reservoirs. There is a need to comprehensively understand these host factors to develop a strategy to cure HIV infection and prevent viral rebound post-ART. Lipids are important biologically active molecules that are known to mediate several cellular functions, including reactivating latent tumor cells; however, their role in HIV latency, persistence, and post-ART rebound has never been investigated. We observed significant links between higher levels of the pro-inflammatory lysophosphatidylcholine and its intestinal metabolic byproduct, trimethylamine-N-oxide, and both faster time-to-viral rebound and higher viral load setpoint post ART. These data highlight the need for further studies to understand the potential contribution of phosphatidylcholine and lysophosphatidylcholine metabolism in shaping host immunological and inflammatory milieu during- and post-ART.

scholarly journals 4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation

2020 ◽  
Vol 4 (s1) ◽  
pp. 11-11
Author(s):  
Tyler Nguyen ◽  
Zoe Vriesman ◽  
Peter Andrews ◽  
Sehban Masood ◽  
M Stewart ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Post Treatment ◽  
Calcium Signals ◽  
Whole Brain ◽  
Non Invasive ◽  
Cortical Regions

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.

scholarly journals Increased proviral DNA in circulating cells correlates with plasma viral rebound in SIV-infected rhesus macaques after antiretroviral therapy interruption

2021 ◽  
Author(s):  
Widade Ziani ◽  
Jiasheng Shao ◽  
Xiaolei Wang ◽  
Kasi Russell-Lodrigue ◽  
Yao-Zhong Liu ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Rhesus Macaques ◽  
Treatment Interruption ◽  
Post Treatment ◽  
Major Obstacle ◽  
People Living With Hiv ◽  
Viral Rebound ◽  
Viral Dna ◽  
Proviral Dna ◽  
Therapy Interruption

The HIV reservoir is responsible for persistent viral infection, and a small number of mosaic latent cellular reservoirs promote viral rebound upon antiretroviral therapy interruption, which is the major obstacle to a cure. However, markers that determine effective therapy and viral rebound post-treatment interruption remain unclear. Here we comprehensively and longitudinally tracked dynamic decay of cell-associated viral RNA/DNA in systemic and lymphoid tissues in SIV-infected rhesus macaques on prolonged combined antiretroviral therapy (cART) and evaluated predictors of viral rebound after treatment cessation. The results showed that suppressive ART substantially reduced plasma SIV RNA, cell-associated unspliced, and multiply spliced SIV RNA to undetectable levels, yet viral DNA remained detectable in systemic tissues and lymphoid compartments throughout cART. Intriguingly, a rapid increase of integrated proviral DNA in peripheral mononuclear cells was detected once treatment was withdrawn, accompanied by the emergence of detectable plasma viral load. Notably, the increase of peripheral proviral DNA post treatment interruption correlated with the emergence and degree of viral rebound. These findings suggest that measuring total viral DNA in SIV infection may be a relatively simple surrogate marker of reservoir size, and may predict viral rebound after treatment interruption, and inform treatment strategies. Importance Viral reservoirs are involved in persistent HIV infection, and a small number of mosaic latent cellular reservoirs promote viral rebound upon analytical treatment interruption, which are the major obstacle to a cure. However, early indicators that can predict resurgence of viremia after treatment interruption may aid treatment decisions in people living with HIV. Utilizing the rhesus macaque model, here we demonstrate increased proviral DNA in peripheral cells after treatment interruption, rather than levels of proviral DNA, was a useful marker to predict the emergence and degree of viral rebound after treatment interruption, providing a rapid approach for monitoring HIV rebound and informing decisions.

scholarly journals Phospholipid Metabolism Is Associated with Time to HIV Rebound upon Treatment Interruption

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leila B. Giron ◽  
Emmanouil Papasavvas ◽  
Xiangfan Yin ◽  
Aaron R. Goldman ◽  
Hsin-Yao Tang ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Tumor Cells ◽  
Treatment Interruption ◽  
Phospholipid Metabolism ◽  
Biologically Active ◽  
Inflammatory Factors ◽  
Hiv Latency ◽  
Potential Contribution ◽  
Viral Rebound

ABSTRACT Lipids are biologically active molecules involved in a variety of cellular processes and immunological functions, including inflammation. It was recently shown that phospholipids and their derivatives, lysophospholipids, can reactivate latent (dormant) tumor cells, causing cancer recurrence. However, the potential link between lipids and HIV latency, persistence, and viral rebound after cessation of antiretroviral therapy (ART) has never been investigated. We explored the links between plasma lipids and the burden of HIV during ART. We profiled the circulating lipidome from plasma samples from 24 chronically HIV-infected individuals on suppressive ART who subsequently underwent an analytic treatment interruption (ATI) without concurrent immunotherapies. The pre-ATI viral burden was estimated as time-to-viral-rebound and viral load set points post-ATI. We found that higher pre-ATI levels of lysophospholipids, including the proinflammatory lysophosphatidylcholine, were associated with faster time-to-viral-rebound and higher viral set points upon ART cessation. Furthermore, higher pre-ATI levels of the proinflammatory by-product of intestinal lysophosphatidylcholine metabolism, trimethylamine-N-oxide (TMAO), were also linked to faster viral rebound post-ART. Finally, pre-ATI levels of several phosphatidylcholine species (lysophosphatidylcholine precursors) correlated strongly with higher pre-ATI levels of HIV DNA in peripheral CD4+ T cells. Our proof-of-concept data point to phospholipids and lysophospholipids as plausible proinflammatory contributors to HIV persistence and rapid post-ART HIV rebound. The potential interplay between phospholipid metabolism and both the establishment and maintenance of HIV latent reservoirs during and after ART warrants further investigation. IMPORTANCE The likelihood of HIV rebound after stopping antiretroviral therapy (ART) is a combination of the size of HIV reservoirs that persist despite ART and the host immunological and inflammatory factors that control these reservoirs. Therefore, there is a need to comprehensively understand these host factors to develop a strategy to cure HIV infection and prevent viral rebound post-ART. Lipids are important biologically active molecules that are known to mediate several cellular functions, including reactivating latent tumor cells; however, their role in HIV latency, persistence, and post-ART rebound has never been investigated. We observed significant links between higher levels of the proinflammatory lysophosphatidylcholine and its intestinal metabolic by-product, trimethylamine-N-oxide, and both faster time-to-viral-rebound and higher viral load set point post-ART. These data highlight the need for further studies to understand the potential contribution of phosphatidylcholine and lysophosphatidylcholine metabolism in shaping host immunological and inflammatory milieu during and after ART.

Follicular fluid and assisted reproductive technology programs outcomes (literature review)

GYNECOLOGY ◽  
2020 ◽  
Vol 21 (6) ◽  
pp. 36-40
Author(s):  
Anna G. Burduli ◽  
Natalia A. Kitsilovskaya ◽  
Yuliya V. Sukhova ◽  
Irina A. Vedikhina ◽  
Tatiana Y. Ivanets ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Assisted Reproductive Technology ◽  
Follicular Fluid ◽  
Economic Cost ◽  
Reproductive Technology ◽  
Art Programs ◽  
Vitro Fertilization ◽  
Non Invasive ◽  
Established Fact

The review presents data on metabolites in the follicular fluid (FF) from the perspective of reproductive medicine and their use in order to predict outcomes of assisted reproductive technology (ART) programs. It considers various components of this biological medium (hormones, lipids, melatonin, etc.) with an assessment of their predictive value in prognosis of the effectiveness of in vitro fertilization (IVF) programs. The data on experimental directions in this field and the prospects for their use in clinical practice are presented. The article emphasizes that the growing clinical need and the unsolved problem of increasing the effectiveness of ART programs determine the need for further studies of the FF composition. Materials and methods. The review includes data related to this topic from foreign and Russian articles found in PubMed which were published in recent years. Results. Given the established fact of a direct effect of FF composition on growth and maturation of oocytes, and further, on the fertilization process, various FF metabolites are actively investigated as non-invasive markers of quality of oocytes/embryos. The article provides data on the experimental directions in this field and the prospects for their use in clinical practice. However, clinical studies of a relation between various FF metabolites levels and outcomes of IVF programs are contradictory. Conclusion. Owing large economic cost for treatment of infertility with IVF, there is need for expansion and intensification of studies to identify and use reliable predictors in prognosis of ART programs outcomes.

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