Stochastic population switch may explain the latent reservoir stability and intermittent viral blips in HIV patients on suppressive therapy

Wang, Sunpeng; Liang, Rong

doi:10.1016/j.jtbi.2014.06.042

Cited by 31 publications

(22 citation statements)

References 76 publications

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“…Some other models studying the dynamics of the latent reservoir and low-level viral load persistence during effective antiretroviral therapy can be found in refs. [2,14,48,50] and references cited therein. Reviews of mathematical models and implications for treatment can be found in refs.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Analysis of HIV models with two time delays

Alshorman

Wang

Meyer

et al. 2016

Journal of Biological Dynamics

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Time delays can affect the dynamics of HIV infection predicted by mathematical models. In this paper, we studied two mathematical models each with two time delays. In the first model with HIV latency, one delay is the time between viral entry into a cell and the establishment of HIV latency, and the other delay is the time between cell infection and viral production. We defined the basic reproductive number and showed the local and global stability of the steady states. Numerical simulations were performed to evaluate the influence of time delays on the dynamics. In the second model with HIV immune response, one delay is the time between cell infection and viral production, and the other delay is the time needed for the adaptive immune response to emerge to control viral replication. With two positive delays, we obtained the stability crossing curves for the model, which were shown to be a series of open-ended curves. ARTICLE HISTORY

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Section: Conclusion and Discussionmentioning

confidence: 99%

Analysis of HIV models with two time delays

Alshorman

Wang

Meyer

et al. 2016

Journal of Biological Dynamics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Among them are the activation of long-lived latent cells, occasional activation of the immune system due to vaccines or secondary infections, or intrinsic within host mechanisms [9, 6, 7, 8, 48, 49, 50]. Intrinsic mechanism in the within host infection dynamics may contribute to the formation of viral blips as presented in [50].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, as a main contribution they presented that within host dynamics may also contribute to the formation of blips, apart from exogenous sources. On the other hand, other mathematical studies introduce exogenous sources (for example the activation of latent cells) to trigger the formation of a viral blip [9, 6, 7, 8, 48, 49]. In these models, the exogenous source is modeled as events that are discrete, random and with different strength.…”

Section: Discussionmentioning

confidence: 99%

Increased inflammation in sanctuary sites may explain viral blips in HIV infection

2016

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Combined antiretroviral therapy (cART) is a powerful therapy to suppress HIV-1 viral replication. Although in treatment, viral load in plasma remains below the limit of detection in regular assays, 50copiesmL, intermittent episodes of transient viremia (viral blips) over the limit of detection occur in a significant set of HIV-patients under cART. Here, we develop a model-based study of a possible relation between ongoing replication in lymphoid-tissue-based sanctuary sites and viral blips. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, we hypothesize that when the diameter of the lymph node follicle increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To demonstrate this we do a theoretical analysis of the model to find those conditions that guarantee that the virus is suppressed in all compartments, and simulate the model for different scenarios of lymph node follicle diameter changes. Thus, to have realistic viral blips, with duration of less than 30 days and with amplitudes relatively close to the limit of detection, the diameter rise rate should be between 0.02 and 0.03 days−1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the steady state viral load after the blip is below the limit of detection, the median value of R0 is 1.45. However, when the median increases beyond 2.1, the steady state of the viral load after the blip often has a value above the limit of detection if the final maximum diameter is sufficiently small. In these cases, for a realistic blip, the maximum final diameters should be greater than 0.7mm so that there is a relative loss of connection between compartments.

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“…This phenomenon has been attributed to changes in viral reservoir stability, and has been modeled using stochastic models (73). These blips might be responsible for the ongoing inflammation and damage observed in chronic infection, such that the infected patient's viremia is never truly stably undetectable.…”

Section: Introductionmentioning

confidence: 99%

Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)

2015

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Early in the HIV epidemic, the central nervous system (CNS) was recognized as a target of infection and injury in the advanced stages of disease. Though the most severe forms of HIV-associated neurocognitive disorder (HAND) related to severe immunosuppression are rare in the current era of widespread combination antiretroviral therapy (cART), evidence now supports pathological involvement of the CNS throughout the course of infection. Recent work suggests that the stage for HIV neuropathogenesis may be set with initial viral entry into the CNS, followed by initiation of pathogenetic processes including neuroinflammation and neurotoxicity, and establishment of local, compartmentalized HIV replication that may reflect a tissue reservoir for HIV. Key questions still exist as to when HIV establishes local infection in the CNS, which CNS cells are the primary targets of HIV, and what mechanistic processes underlie the injury to neurons that produce clinical symptoms of HAND. Advances in these areas will provide opportunities for improved treatment of patients with established HAND, prevention of neurological disease in those with early stage infection, and understanding of HIV tissue reservoirs that will aid efforts at HIV eradication.

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Stochastic population switch may explain the latent reservoir stability and intermittent viral blips in HIV patients on suppressive therapy

Cited by 31 publications

References 76 publications

Analysis of HIV models with two time delays

Analysis of HIV models with two time delays

Increased inflammation in sanctuary sites may explain viral blips in HIV infection

Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)

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