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A study on the dynamics of temporary HIV treatment to assess the controversial outcomes of clinical trials: An in-silico approach

Mancini, E; Quax, R; De Luca, A; Fidler, S; Stohr, W; Sloot, PMA; (2018) A study on the dynamics of temporary HIV treatment to assess the controversial outcomes of clinical trials: An in-silico approach. PLoS One , 13 (7) , Article e0200892. 10.1371/journal.pone.0200892. Green open access

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Abstract

It is still unclear under which conditions temporary combined antiretroviral therapy (cART) results in a prolonged remission after interruption. Clinical trials have contradicting reposts about the effect of cART during primary HIV infection on the disease progression. Here we propose that the apparent contradiction is due the presence of a window of opportunity for cART treatment observed in the in silico studies. We study non-linear correlations in the HIV dynamics over time using information theory. This approach requires a large dataset of CD4+ T lymphocytes and viral load concentrations over time. Since it is unfeasible to collect the required amount of data in clinical trials we use C-ImmSim, a clinically validated in silico model of the HIV infection, to simulate the HIV infection and temporary cART in 500 virtual patients for a period of 6 years post infection in time steps of 8 hours. We validate the results of our model with two published clinical trials of temporary cART in acute infection and analyse the impact of cART on the immune response. Our quantitative analysis predicts a “window of opportunity” of about ten months after the acute phase during which a temporary cART has significantly longer-lasting beneficial effects on the immune system as compared to treatment during the chronic phase. This window may help to explain the controversial outcomes of clinical trials that differ by the starting time and duration of the short-term course cART and provides a critical insight to develop appropriate protocols for future clinical trials.

Type: Article
Title: A study on the dynamics of temporary HIV treatment to assess the controversial outcomes of clinical trials: An in-silico approach
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0200892
Publisher version: https://doi.org/10.1371/journal.pone.0200892
Language: English
Additional information: © 2018 Mancini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: HIV, HIV infections, Immune response, Immune system, Viral load, Clinical trials, Lymph nodes, Lymphocytes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10053475
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