Analysis of an HIV model with post-treatment control

AbstractRecent investigation indicated that latent reservoir and immune impairment are responsible for the post-treatment control of HIV infection. In this paper, we simplify the disease model with latent reservoir and immune impairment and perform a series of mathematical analysis. We obtain the basic infection reproductive number R0 to characterize the viral dynamics. We prove that when R0 < 1, the uninfected equilibrium of the proposed model is globally asymptotically stable. When R0 > 1, we obtain two thresholds, the post-treatment immune control threshold and the elite control threshold. The model has bistable behaviors in the interval between the two thresholds. If the proliferation rate of CTLs is less than the post-treatment immune control threshold, the model does not have positive equilibria. In this case, the immune free equilibrium is stable and the system will have virus rebound. On the other hand, when the proliferation rate of CTLs is greater than the elite control threshold, the system has stable positive immune equilibrium and unstable immune free equilibrium. Thus, the system is under elite control.Author summaryIn this article, we use mathematical model to investigate the combined effect of latent reservoir and immune impairment on the post-treatment control of HIV infection. By simplifying an HIV model with latent reservoir and immune impairment, and performing mathematical analysis, we obtain the post-treatment immune control threshold and the elite control threshold for the HIV dynamics when R0 > 1. The HIV model displays bistable behaviors in the interval between the two thresholds. We illustrate our results using both mathematical analysis and numerical simulation. Our result is consistent with recent medical experiment. We show that patient with low proliferation rate of CTLs may undergo virus rebound, and patient with high proliferation rate of CTLs may obtain elite control of HIV infection. We perform bifurcation analysis to illustrate the infection status of patient with the variation of proliferation rate of CTLs, which potentially explain the reason behind different outcomes among HIV patients.

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

Nature Communications ◽

10.1038/s41467-021-24077-w ◽

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.

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Frequency of Post Treatment Control Varies by ART Restart and Viral Load Criteria

AIDS ◽

10.1097/qad.0000000000002978 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Jesse Fajnzylber ◽

Radwa Sharaf ◽

John N. Hutchinson ◽

Evgenia Aga ◽

Ronald J. Bosch ◽

...

Keyword(s):

Viral Load ◽

Post Treatment ◽

Treatment Control

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

Journal of Virus Eradication ◽

10.1016/s2055-6640(20)30949-3 ◽

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

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Broadly neutralising antibodies in post-treatment control

The Lancet HIV ◽

10.1016/s2352-3018(19)30075-x ◽

2019 ◽

Vol 6 (5) ◽

pp. e271-e272 ◽

Cited By ~ 1

Author(s):

Godelieve J de Bree ◽

Rogier W Sanders

Keyword(s):

Post Treatment ◽

Treatment Control ◽

Neutralising Antibodies

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Models of increased latent HIV reservoir turnover prior to cART initiation imply novel clearance strategies

10.1101/2021.06.06.447292 ◽

2021 ◽

Author(s):

Aditya Jagarapu ◽

Rajveer Mann ◽

Michael J Piovoso ◽

Ryan Zurakowski

Keyword(s):

Immune Response ◽

T Cells ◽

Antiretroviral Therapy ◽

Half Life ◽

Post Treatment ◽

Latent Reservoir ◽

Treatment Control ◽

Hiv Reservoir ◽

Treatment Interruptions ◽

Exogenous Antigen

CD4+ T cells with a naive or memory phenotype carrying a replication-competent HIV provirus are recognized as the major component of the persistent HIV reservoir. These cells only mini- mally express viral protein, reducing viral cytotoxicity effects and making them difficult targets for immune responses as well as every available antiretroviral drug. In patients on suppressive antiretroviral therapy, the half-life of these cells is approximately 4-5 years, balanced by clonal expansion of the cells resulting in an overall reservoir half-life in excess of 40 years. A recent study has shown that prior to the initiation of antiretroviral therapy, the half-life of these cells is instead on the order of two weeks. We present two models explaining the wide disparity in the on- and off-treatment half-lives of the quiescent infected T cells. In the first model, generalized (antigen non-specific) immune activation due to the high HIV viral loads explains the high latent reservoir turnover rates in the absence of treatment. If this mechanism dominates, we demon- strate that reduction of the latent reservoir size is possible, either through the administration of exogenous antigen or through the use of timed treatment interruptions. In the second model, direct killing of reservoir cells by HIV drives the increased turnover off-treatment. If this mecha- nism dominates, modulation of the reservoir size is not possible by the methods described above. Previously published models of the immune response to HIV show the possibility of inducing post-treatment control by reducing the latent reservoir size; by incorporating the same immune response dynamics in our first model, it is shown that it may be possible to induce post-treatment control using either exogenous antigen administration or timed treatment interruptions.

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Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection

AIDS ◽

10.1097/qad.0000000000001382 ◽

2017 ◽

Vol 31 (4) ◽

pp. 477-484 ◽

Cited By ~ 31

Author(s):

Genevieve E. Martin ◽

Morgane Gossez ◽

James P. Williams ◽

Wolfgang Stöhr ◽

Jodi Meyerowitz ◽

...

Keyword(s):

Hiv Infection ◽

Post Treatment ◽

Treatment Control ◽

Primary Hiv Infection

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Post-treatment control of HIV infection

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1419162112 ◽

2015 ◽

Vol 112 (17) ◽

pp. 5467-5472 ◽

Cited By ~ 93

Author(s):

Jessica M. Conway ◽

Alan S. Perelson

Keyword(s):

Hiv Infection ◽

Primary Infection ◽

Population Level ◽

Post Treatment ◽

Latent Reservoir ◽

Target Cells ◽

Elite Controllers ◽

Treatment Control ◽

Treatment Termination ◽

Infected Cells

Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infected cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.

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Anger, Arousal, and Systematic Desensitization

Psychological Reports ◽

10.2466/pr0.1973.32.2.625 ◽

1973 ◽

Vol 32 (2) ◽

pp. 625-626 ◽

Cited By ~ 9

Author(s):

David R. Evans ◽

Margaret T. Hearn ◽

Donald Saklofske

Keyword(s):

Nursing Students ◽

Physiological Responses ◽

Post Treatment ◽

Control Group ◽

Systematic Desensitization ◽

Treatment Control ◽

Anger Arousal ◽

Treatment Control Group

The effect of systematic desensitization on semantic and physiological responses to anger-inducing scenes was examined with 20 nursing students. Pre- and post-treatment GSR, and semantic responses of a treatment and a no-treatment control group were obtained during exposure to anger-inducing scenes. Results supported the hypothesis that systematic desensitization reduces arousal and rated anger to the scenes.

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