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HIV infection dynamics and viral rebound: Modeling results from humanized mice.
- Source :
-
Journal of Theoretical Biology . Jun2023, Vol. 567, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Despite years of combined antiretroviral therapy (cART), HIV persists in infected individuals. The virus also rebounds after the cessation of cART. The sources contributing to viral persistence and rebound are not fully understood. When viral rebound occurs, what affects the time to rebound and how to delay the rebound remain unclear. In this paper, we started with the data fitting of an HIV infection model to the viral load data in treated and untreated humanized myeloid-only mice (MoM) in which macrophages serve as the target of HIV infection. By fixing the parameter values for macrophages from the MoM fitting, we fit a mathematical model including the infection of two target cell populations to the viral load data from humanized bone marrow/liver/thymus (BLT) mice, in which both CD4+ T cells and macrophages are the target of HIV infection. Data fitting suggests that the viral load decay in BLT mice under treatment has three phases. The loss of infected CD4+ T cells and macrophages is a major contributor to the first two phases of viral decay, and the last phase may be due to the latent infection of CD4+ T cells. Numerical simulations using parameter estimates from the data fitting show that the pre-ART viral load and the latent reservoir size at treatment cessation can affect viral growth rate and predict the time to viral rebound. Model simulations further reveal that early and prolonged cART can delay the viral rebound after cessation of treatment, which may have implications in the search for functional control of HIV infection. • A macrophage infection model is fit to humanized myeloid-only (MoM) mouse data. • A model with two targets of HIV infection is fit to humanized BLT mouse data. • We studied the viral load decay dynamics in BLT mice under treatment. • We evaluated what might cause a rapid viral rebound after treatment cessation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV infections
*VIRUS diseases
*LATENT infection
*VIRAL load
*BONE marrow
*HIV
Subjects
Details
- Language :
- English
- ISSN :
- 00225193
- Volume :
- 567
- Database :
- Academic Search Index
- Journal :
- Journal of Theoretical Biology
- Publication Type :
- Academic Journal
- Accession number :
- 163551561
- Full Text :
- https://doi.org/10.1016/j.jtbi.2023.111490