Antiretroviral therapy suppressed participants withlow CD4RT-cell counts segregate according toopposite immunological phenotypes
Author
Pérez-Santiago, Josué
Ouchi, Dan
Urrea, Victor
Carrillo, Jorge
Cabrera, Cecilia
Villà-Freixa, Jordi
Puig, Jordi
Paredes, Roger
Negredo, Eugènia
Clotet, Bonaventura
Massanella, Marta
Blanco, Julià
Publication date
2016-09ISSN
0269-9370
Abstract
Background:The failure to increase CD4þT-cell counts in some antiretroviral therapysuppressed participants (immunodiscordance) has been related to perturbed CD4þT-cell homeostasis and impacts clinical evolution.Methods:We evaluated different definitions of immunodiscordance based on CD4þT-cell counts (cutoff) or CD4þT-cell increases from nadir value (DCD4) using super-vised random forest classification of 74 immunological and clinical variables from 196antiretroviral therapy suppressed individuals. Unsupervised clustering was performedusing relevant variables identified in the supervised approach from 191 individuals.Results:Cutoff definition of CD4þcell count 400 cells/ml performed better than anyother definition in segregating immunoconcordant and immunodiscordant individuals(85% accuracy), using markers of activation, nadir and death of CD4þT cells.Unsupervised clustering of relevant variables using this definition revealed largeheterogeneity between immunodiscordant individuals and segregated participants intothree distinct subgroups with distinct production, programmed cell-death protein-1(PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible numberof immunodiscordant participants (22%) showed high frequency of recent thymicemigrants and low CD4þT-cell activation and death, very similar to immunoconcor-dant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR)PD-1 and CD45RA expression in CD4þT cells allowed reproducing subgroup segre-gation (81.4% accuracy). Despite sharp immunological differences, similar andpersistently low CD4þvalues were maintained in these participants over time.Conclusion:A cutoff value of CD4þT-cell count 400 cells/ml classified betterimmunodiscordant and immunoconcordant individuals than anyDCD4 classification.Immunodiscordance may present several, even opposite, immunological patterns thatare identified by a simple immunological follow-up. Subgroup classification may helpclinicians to delineate diverse approaches that may be needed to boost CD4þT-cellrecovery.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Mort cel·lular
Resposta immunitària
Homeòstasi
Antiretrovirals
Metge i pacient
Muerte celular
Respuesta inmune
Homeostasis
Antirretrovirales
Médicos y pacientes
Cell death
Immune response
Homeostasis
Antiretrovirals
Doctor and patient
Pages
13
Publisher
Wolters Kluwer
Collection
30;15
Is part of
AIDS
Citation
Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor [et al.]. Antiretroviral therapy suppressed participants withlow CD4RT-cell counts segregate according toopposite immunological phenotypes. AIDS, 2016, 30(15), p. 2275-2287. Disponible en: <https://journals.lww.com/aidsonline/Fulltext/2016/09240/Antiretroviral_therapy_suppressed_participants.4.aspx>. Fecha de acceso: 28 oct. 2020. DOI: 10.1097/QAD.0000000000001205
This item appears in the following Collection(s)
- Ciències de la Salut [712]
Rights
2016 Wolters Kluwer Health, Inc. All rights reserved. This is an open-access article distributed under the termsof the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the workprovided it is properly cited. The work cannot be changed in any way or used commercially.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/