Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy.
Although potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient ep...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-10-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC2752194?pdf=render |
| _version_ | 1818146350074691584 |
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| author | Libin Rong Alan S Perelson |
| author_facet | Libin Rong Alan S Perelson |
| author_sort | Libin Rong |
| collection | DOAJ |
| description | Although potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit, termed viral blips, even after being on highly suppressive therapy for many years. An obstacle to viral eradication is the persistence of a latent reservoir for HIV-1 in resting memory CD4(+) T cells. The mechanisms underlying low viral load persistence, slow decay of the latent reservoir, and intermittent viral blips are not fully characterized. The quantitative contributions of residual viral replication to viral and the latent reservoir persistence remain unclear. In this paper, we probe these issues by developing a mathematical model that considers latently infected cell activation in response to stochastic antigenic stimulation. We demonstrate that programmed expansion and contraction of latently infected cells upon immune activation can generate both low-level persistent viremia and intermittent viral blips. Also, a small fraction of activated T cells revert to latency, providing a potential to replenish the latent reservoir. By this means, occasional activation of latently infected cells can explain the variable decay characteristics of the latent reservoir observed in different clinical studies. Finally, we propose a phenomenological model that includes a logistic term representing homeostatic proliferation of latently infected cells. The model is simple but can robustly generate the multiphasic viral decline seen after initiation of therapy, as well as low-level persistent viremia and intermittent HIV-1 blips. Using these models, we provide a quantitative and integrated prospective into the long-term dynamics of HIV-1 and the latent reservoir in the setting of potent antiretroviral therapy. |
| first_indexed | 2024-12-11T12:17:57Z |
| format | Article |
| id | doaj.art-34aae7fd6d2b4eebb5d2fc8738bad832 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-11T12:17:57Z |
| publishDate | 2009-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-34aae7fd6d2b4eebb5d2fc8738bad8322022-12-22T01:07:36ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582009-10-01510e100053310.1371/journal.pcbi.1000533Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy.Libin RongAlan S PerelsonAlthough potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit, termed viral blips, even after being on highly suppressive therapy for many years. An obstacle to viral eradication is the persistence of a latent reservoir for HIV-1 in resting memory CD4(+) T cells. The mechanisms underlying low viral load persistence, slow decay of the latent reservoir, and intermittent viral blips are not fully characterized. The quantitative contributions of residual viral replication to viral and the latent reservoir persistence remain unclear. In this paper, we probe these issues by developing a mathematical model that considers latently infected cell activation in response to stochastic antigenic stimulation. We demonstrate that programmed expansion and contraction of latently infected cells upon immune activation can generate both low-level persistent viremia and intermittent viral blips. Also, a small fraction of activated T cells revert to latency, providing a potential to replenish the latent reservoir. By this means, occasional activation of latently infected cells can explain the variable decay characteristics of the latent reservoir observed in different clinical studies. Finally, we propose a phenomenological model that includes a logistic term representing homeostatic proliferation of latently infected cells. The model is simple but can robustly generate the multiphasic viral decline seen after initiation of therapy, as well as low-level persistent viremia and intermittent HIV-1 blips. Using these models, we provide a quantitative and integrated prospective into the long-term dynamics of HIV-1 and the latent reservoir in the setting of potent antiretroviral therapy.http://europepmc.org/articles/PMC2752194?pdf=render |
| spellingShingle | Libin Rong Alan S Perelson Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLoS Computational Biology |
| title | Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. |
| title_full | Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. |
| title_fullStr | Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. |
| title_full_unstemmed | Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. |
| title_short | Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. |
| title_sort | modeling latently infected cell activation viral and latent reservoir persistence and viral blips in hiv infected patients on potent therapy |
| url | http://europepmc.org/articles/PMC2752194?pdf=render |
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