HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.

Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity co...

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Autores principales:	Emiliano Mancini, Filippo Castiglione, Massimo Bernaschi, Andrea de Luca, Peter M A Sloot
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a258475ab584ab79fb51b1ba242ab67
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spelling	oai:doaj.org-article:0a258475ab584ab79fb51b1ba242ab672021-11-18T07:20:26ZHIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.1932-620310.1371/journal.pone.0036108https://doaj.org/article/0a258475ab584ab79fb51b1ba242ab672012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558348/?tool=EBIhttps://doaj.org/toc/1932-6203Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.Emiliano ManciniFilippo CastiglioneMassimo BernaschiAndrea de LucaPeter M A SlootPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e36108 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emiliano Mancini Filippo Castiglione Massimo Bernaschi Andrea de Luca Peter M A Sloot HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
description	Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.
format	article
author	Emiliano Mancini Filippo Castiglione Massimo Bernaschi Andrea de Luca Peter M A Sloot
author_facet	Emiliano Mancini Filippo Castiglione Massimo Bernaschi Andrea de Luca Peter M A Sloot
author_sort	Emiliano Mancini
title	HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
title_short	HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
title_full	HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
title_fullStr	HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
title_full_unstemmed	HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
title_sort	hiv reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0a258475ab584ab79fb51b1ba242ab67
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HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.

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