eprintid: 10053475
rev_number: 21
eprint_status: archive
userid: 608
dir: disk0/10/05/34/75
datestamp: 2018-07-31 12:04:15
lastmod: 2021-10-04 00:02:44
status_changed: 2018-07-31 12:04:15
type: article
metadata_visibility: show
creators_name: Mancini, E
creators_name: Quax, R
creators_name: De Luca, A
creators_name: Fidler, S
creators_name: Stohr, W
creators_name: Sloot, PMA
title: A study on the dynamics of temporary HIV treatment to assess the controversial outcomes of clinical trials: An in-silico approach
ispublished: pub
divisions: UCL
divisions: B02
divisions: C09
divisions: D65
divisions: J38
keywords: HIV, HIV infections, Immune response, Immune system, Viral load, Clinical trials, Lymph nodes, Lymphocytes
note: © 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/).
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.
date: 2018-07-18
date_type: published
official_url: https://doi.org/10.1371/journal.pone.0200892
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1571572
doi: 10.1371/journal.pone.0200892
pii: PONE-D-17-34102
language_elements: English
lyricists_name: Stohr, Wolfgang
lyricists_id: WSTOH63
actors_name: Stohr, Wolfgang
actors_id: WSTOH63
actors_role: owner
full_text_status: public
publication: PLoS One
volume: 13
number: 7
article_number: e0200892
event_location: United States
issn: 1932-6203
citation:        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 <https://doi.org/10.1371/journal.pone.0200892>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10053475/1/Stohr_A%20study%20on%20the%20dynamics%20of%20temporary%20HIV%20treatment%20to%20assess%20the%20controversial%20outcomes%20of%20clinical%20trials.%20An%20in-silico%20approach_VoR.pdf