Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Abstract Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain...

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Autores principales:	Concepcion Casado, Cristina Galvez, Maria Pernas, Laura Tarancon-Diez, Carmen Rodriguez, Víctor Sanchez-Merino, Mar Vera, Isabel Olivares, Rebeca De Pablo-Bernal, Alberto Merino-Mansilla, Jorge Del Romero, Ramon Lorenzo-Redondo, Ezequiel Ruiz-Mateos, María Salgado, Javier Martinez-Picado, Cecilio Lopez-Galindez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9afa80bdaabf490c8c3d29884df46882
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spelling	oai:doaj.org-article:9afa80bdaabf490c8c3d29884df468822021-12-02T14:06:58ZPermanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure10.1038/s41598-020-58696-y2045-2322https://doaj.org/article/9afa80bdaabf490c8c3d29884df468822020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-58696-yhttps://doaj.org/toc/2045-2322Abstract Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/106 CD4+ T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.Concepcion CasadoCristina GalvezMaria PernasLaura Tarancon-DiezCarmen RodriguezVíctor Sanchez-MerinoMar VeraIsabel OlivaresRebeca De Pablo-BernalAlberto Merino-MansillaJorge Del RomeroRamon Lorenzo-RedondoEzequiel Ruiz-MateosMaría SalgadoJavier Martinez-PicadoCecilio Lopez-GalindezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Concepcion Casado Cristina Galvez Maria Pernas Laura Tarancon-Diez Carmen Rodriguez Víctor Sanchez-Merino Mar Vera Isabel Olivares Rebeca De Pablo-Bernal Alberto Merino-Mansilla Jorge Del Romero Ramon Lorenzo-Redondo Ezequiel Ruiz-Mateos María Salgado Javier Martinez-Picado Cecilio Lopez-Galindez Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
description	Abstract Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/106 CD4+ T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.
format	article
author	Concepcion Casado Cristina Galvez Maria Pernas Laura Tarancon-Diez Carmen Rodriguez Víctor Sanchez-Merino Mar Vera Isabel Olivares Rebeca De Pablo-Bernal Alberto Merino-Mansilla Jorge Del Romero Ramon Lorenzo-Redondo Ezequiel Ruiz-Mateos María Salgado Javier Martinez-Picado Cecilio Lopez-Galindez
author_facet	Concepcion Casado Cristina Galvez Maria Pernas Laura Tarancon-Diez Carmen Rodriguez Víctor Sanchez-Merino Mar Vera Isabel Olivares Rebeca De Pablo-Bernal Alberto Merino-Mansilla Jorge Del Romero Ramon Lorenzo-Redondo Ezequiel Ruiz-Mateos María Salgado Javier Martinez-Picado Cecilio Lopez-Galindez
author_sort	Concepcion Casado
title	Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
title_short	Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
title_full	Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
title_fullStr	Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
title_full_unstemmed	Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
title_sort	permanent control of hiv-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9afa80bdaabf490c8c3d29884df46882
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Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

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