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Front. Immunol. | doi: 10.3389/fimmu.2019.00025

Thymic Function As a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy

  • 1University of Minho, Portugal
  • 2PT Associate Laboratory ICVS/3B’s, Portugal
  • 3Department of Onco-Hematology, Instituto Português de Oncologia Francisco Gentil, Portugal
  • 4INSERM U1016 Institut Cochin, France
  • 5Center for the National Scientific Research (CNRS), France
  • 6Université Paris Descartes, France
  • 7Columbia University, United States
  • 8Centro Hospitalar do Porto, Portugal
  • 9Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Sweden

Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4+ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4+ T cell count trajectories. Based on a variety of immunological parameters, we built predictive models of PIR/AIR outcome using logistic regression. All PIR had CD4+ T cell counts consistently below 500 cells/µL, while all AIR reached this threshold. AIR showed higher percentage of recent thymic emigrants among CD4+ T cells; higher numbers of sjTRECs and greater sj/βTREC ratios; and significant increases in thymic volume from baseline to 12 months of ART. We identified mathematical models that correctly predicted PIR/AIR outcome after 36 months of therapy in 77-87 % of cases, based on observations made until 2-6 months after ART onset. This study highlights the importance of thymic activity in the immune recovery of severely lymphopenic patients, and may help to select the patients that will benefit from closer follow-up or novel therapeutic approaches.

Keywords: HIV - human immunodeficiency virus, poor immunological responders, predictive modelling, Thymic function, Immune recovery, Antiretroviral therapy (ART), CD4 T cells, immune activation

Received: 08 Oct 2018; Accepted: 07 Jan 2019.

Edited by:

Francesca Chiodi, Karolinska Institute (KI), Sweden

Reviewed by:

Ruy Ribeiro, Los Alamos National Laboratory (DOE), United States
Antonio Bandeira, Centre National de la Recherche Scientifique (CNRS), France  

Copyright: © 2019 Rb-Silva, Nóbrega, Azevedo, Athayde, Gomes, Ferreira, Cheynier, Yates, Horta and Correia-Neves. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Margarida Correia-Neves, University of Minho, Braga, Portugal,