Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound

Abstract Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently...

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Autores principales:	María Rosa López-Huertas, Carolina Gutiérrez, Nadia Madrid-Elena, Beatriz Hernández-Novoa, Julián Olalla-Sierra, Montserrat Plana, Rafael Delgado, Rafael Rubio, María Ángeles Muñoz-Fernández, Santiago Moreno
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Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1d63f1fdd2b4f53a1ec286acb22c2ef
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spelling	oai:doaj.org-article:d1d63f1fdd2b4f53a1ec286acb22c2ef2021-12-02T11:57:56ZProlonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound10.1038/s41598-020-79002-w2045-2322https://doaj.org/article/d1d63f1fdd2b4f53a1ec286acb22c2ef2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79002-whttps://doaj.org/toc/2045-2322Abstract Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.María Rosa López-HuertasCarolina GutiérrezNadia Madrid-ElenaBeatriz Hernández-NovoaJulián Olalla-SierraMontserrat PlanaRafael DelgadoRafael RubioMaría Ángeles Muñoz-FernándezSantiago MorenoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María Rosa López-Huertas Carolina Gutiérrez Nadia Madrid-Elena Beatriz Hernández-Novoa Julián Olalla-Sierra Montserrat Plana Rafael Delgado Rafael Rubio María Ángeles Muñoz-Fernández Santiago Moreno Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
description	Abstract Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.
format	article
author	María Rosa López-Huertas Carolina Gutiérrez Nadia Madrid-Elena Beatriz Hernández-Novoa Julián Olalla-Sierra Montserrat Plana Rafael Delgado Rafael Rubio María Ángeles Muñoz-Fernández Santiago Moreno
author_facet	María Rosa López-Huertas Carolina Gutiérrez Nadia Madrid-Elena Beatriz Hernández-Novoa Julián Olalla-Sierra Montserrat Plana Rafael Delgado Rafael Rubio María Ángeles Muñoz-Fernández Santiago Moreno
author_sort	María Rosa López-Huertas
title	Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
title_short	Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
title_full	Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
title_fullStr	Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
title_full_unstemmed	Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound
title_sort	prolonged administration of maraviroc reactivates latent hiv in vivo but it does not prevent antiretroviral-free viral rebound
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d1d63f1fdd2b4f53a1ec286acb22c2ef
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Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound

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