HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical c...

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Autores principales:	Sergio Serrano-Villar, Talia Sainz, Sulggi A Lee, Peter W Hunt, Elizabeth Sinclair, Barbara L Shacklett, April L Ferre, Timothy L Hayes, Ma Somsouk, Priscilla Y Hsue, Mark L Van Natta, Curtis L Meinert, Michael M Lederman, Hiroyu Hatano, Vivek Jain, Yong Huang, Frederick M Hecht, Jeffrey N Martin, Joseph M McCune, Santiago Moreno, Steven G Deeks
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/34190c80ee49467aaee778896123b3f0
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spelling	oai:doaj.org-article:34190c80ee49467aaee778896123b3f02021-11-18T06:06:35ZHIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.1553-73661553-737410.1371/journal.ppat.1004078https://doaj.org/article/34190c80ee49467aaee778896123b3f02014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24831517/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.Sergio Serrano-VillarTalia SainzSulggi A LeePeter W HuntElizabeth SinclairBarbara L ShacklettApril L FerreTimothy L HayesMa SomsoukPriscilla Y HsueMark L Van NattaCurtis L MeinertMichael M LedermanHiroyu HatanoVivek JainYong HuangFrederick M HechtJeffrey N MartinJoseph M McCuneSantiago MorenoSteven G DeeksPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004078 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sergio Serrano-Villar Talia Sainz Sulggi A Lee Peter W Hunt Elizabeth Sinclair Barbara L Shacklett April L Ferre Timothy L Hayes Ma Somsouk Priscilla Y Hsue Mark L Van Natta Curtis L Meinert Michael M Lederman Hiroyu Hatano Vivek Jain Yong Huang Frederick M Hecht Jeffrey N Martin Joseph M McCune Santiago Moreno Steven G Deeks HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
description	A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
format	article
author	Sergio Serrano-Villar Talia Sainz Sulggi A Lee Peter W Hunt Elizabeth Sinclair Barbara L Shacklett April L Ferre Timothy L Hayes Ma Somsouk Priscilla Y Hsue Mark L Van Natta Curtis L Meinert Michael M Lederman Hiroyu Hatano Vivek Jain Yong Huang Frederick M Hecht Jeffrey N Martin Joseph M McCune Santiago Moreno Steven G Deeks
author_facet	Sergio Serrano-Villar Talia Sainz Sulggi A Lee Peter W Hunt Elizabeth Sinclair Barbara L Shacklett April L Ferre Timothy L Hayes Ma Somsouk Priscilla Y Hsue Mark L Van Natta Curtis L Meinert Michael M Lederman Hiroyu Hatano Vivek Jain Yong Huang Frederick M Hecht Jeffrey N Martin Joseph M McCune Santiago Moreno Steven G Deeks
author_sort	Sergio Serrano-Villar
title	HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
title_short	HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
title_full	HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
title_fullStr	HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
title_full_unstemmed	HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
title_sort	hiv-infected individuals with low cd4/cd8 ratio despite effective antiretroviral therapy exhibit altered t cell subsets, heightened cd8+ t cell activation, and increased risk of non-aids morbidity and mortality.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/34190c80ee49467aaee778896123b3f0
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HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

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