Mathematical modeling of impact of eCD4-Ig molecule in control and management of HIV within a host

Tae Jin Lee; Jose A. Vazquez; Arni S. R. Srinivasa Rao; Tae Jin Lee; Jose A. Vazquez; Arni S. R. Srinivasa Rao

doi:10.3934/mbe.2021342

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 5: 6887-6906. doi: 10.3934/mbe.2021342

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Mathematical modeling of impact of eCD4-Ig molecule in control and management of HIV within a host

1.
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912, USA
2.
Division of Infectious Diseases, Department of Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912, USA
3.
Laboratory for Theory and Mathematical Modeling, Division of Infectious Diseases, Department of Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912, USA
4.
Department of Mathematics, Augusta University, 1120 15th Street, Augusta, GA 30912, USA

Received: 18 June 2021 Accepted: 12 August 2021 Published: 19 August 2021

Eradication and eventually cure of the HIV virus from the infected individual should be the primary goal in all HIV therapy. This has yet to be achieved, however development of broadly neutralizing antibodies (bNabs) and eCD4-Ig and its related particles are promising therapeutic alternatives to eliminate the HIV virus from the host. Past studies have found superior protectivity and efficacy eradicating the HIV virus with the use of eCD4-Igs over bNabs, which has proposed the antibody-dependent cell-mediated cytotoxicity (ADCC) effect as one of the key-factors for antibody design. In this study, we evaluated the dynamics of the HIV virus, CD4 T-cells, and eCD4-Ig in humans using a gene-therapy approach which has been evaluated in primates previously. We utilized a mathematical model to investigate the relationship between eCD4-Ig levels, ADCC effects, and the neutralization effect on HIV elimination. In addition, a balance between ADCC and viral neutralization effect of eCD4-Ig has been investigated in order to understand the condition of which HIV eliminating antibodies needs to satisfy. Our analysis indicated some level of ADCC effect, which was missing from ART, was required for viral elimination. The results will be helpful in designing future drugs or therapeutic strategies.
- HIV,
- eCD4-Ig,
- ODE Model,
- antibody
Citation: Tae Jin Lee, Jose A. Vazquez, Arni S. R. Srinivasa Rao. Mathematical modeling of impact of eCD4-Ig molecule in control and management of HIV within a host[J]. Mathematical Biosciences and Engineering, 2021, 18(5): 6887-6906. doi: 10.3934/mbe.2021342

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Abstract

Eradication and eventually cure of the HIV virus from the infected individual should be the primary goal in all HIV therapy. This has yet to be achieved, however development of broadly neutralizing antibodies (bNabs) and eCD4-Ig and its related particles are promising therapeutic alternatives to eliminate the HIV virus from the host. Past studies have found superior protectivity and efficacy eradicating the HIV virus with the use of eCD4-Igs over bNabs, which has proposed the antibody-dependent cell-mediated cytotoxicity (ADCC) effect as one of the key-factors for antibody design. In this study, we evaluated the dynamics of the HIV virus, CD4 T-cells, and eCD4-Ig in humans using a gene-therapy approach which has been evaluated in primates previously. We utilized a mathematical model to investigate the relationship between eCD4-Ig levels, ADCC effects, and the neutralization effect on HIV elimination. In addition, a balance between ADCC and viral neutralization effect of eCD4-Ig has been investigated in order to understand the condition of which HIV eliminating antibodies needs to satisfy. Our analysis indicated some level of ADCC effect, which was missing from ART, was required for viral elimination. The results will be helpful in designing future drugs or therapeutic strategies.

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