| Title: |
Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy |
| Authors: |
Rb-Silva, R.; Nobrega, C.; Azevedo, C.; Athayde, E.; Canto-Gomes, J.; Ferreira, I.; Cheynier, R.; Yates, A.; Horta, Ana; Correia-Neves, M. |
| Publisher Information: |
Frontiers Media |
| Publication Year: |
2019 |
| Collection: |
Repositório Científico do Centro Hospitalar do Porto |
| Subject Terms: |
CD4+ T cells; HIV infection; antiretroviral therapy; immune activation; immune recovery; poor immunological responders; predictive modeling; thymic function |
| Description: |
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 a higher percentage of recent thymic emigrants among CD4+ T cells; higher numbers of sj-TRECs and greater sj/β TREC 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 the 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. ; This work was supported by: FEDER, through the Competitiveness Factors Operational Program (COMPETE); by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-00(7038) and by Programa Gilead GÉNESE (PGG/018/2017). RR-S and JC-G were supported by FCT grants, in the context of PhDOC—Doctoral Program in Aging and Chronic Diseases (PD/BD/106047/2015 and PD/BD/137433/2018, respectively). CN was also supported by a grant from FCT (SFRH/BPD/112001/2015). CA and EA were partially supported by Portuguese Funds through FCT within the project UID/MAT/00013/2013. AY was supported by Arthritis Research UK. ; info:eu-repo/semantics/publishedVersion |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00025/full; https://hdl.handle.net/10400.16/2381 |
| DOI: |
10.3389/fimmu.2019.00025 |
| Availability: |
https://hdl.handle.net/10400.16/2381; https://doi.org/10.3389/fimmu.2019.00025 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D02707D0 |
| Database: |
BASE |