scholarly journals Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Pierre Frange ◽  
Thomas Montange ◽  
Jérôme Le Chenadec ◽  
Damien Batalie ◽  
Ingrid Fert ◽  
...  

BackgroundThe early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).MethodsThe ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.ResultsAt the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.ConclusionIn children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02674867.

Retrovirology ◽  
2009 ◽  
Vol 6 (S3) ◽  
Author(s):  
S Fonseca ◽  
A Coutinho-Silva ◽  
D Rodrigues ◽  
L Marti ◽  
C Moreira-Filho ◽  
...  

The Lancet ◽  
2003 ◽  
Vol 362 (9401) ◽  
pp. 2045-2051 ◽  
Author(s):  
Chang-Heok Soh ◽  
James M Oleske ◽  
Michael T Brady ◽  
Stephen A Spector ◽  
William Borkowsky ◽  
...  

2014 ◽  
Vol 56 (3) ◽  
pp. 205-211 ◽  
Author(s):  
Cynara Carvalho Nunes ◽  
Maria Cristina Cotta Matte ◽  
Claudia Fontoura Dias ◽  
Leonardo Augusto Luvison Araújo ◽  
Luciano Santos Pinto Guimarães ◽  
...  

Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.


2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
J. Dazley ◽  
R. Sison ◽  
J. Slim

The long-term impact of pegylated-interferon plus ribavirin treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus and hepatitis C virus is largely unclear in the literature. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy. We retrospectively enrolled HIV/HCV-coinfected patients on HIV medications and treated for hepatitis C. CD4 + T cell counts were registered at baseline and after hepatitis C therapy. Multiple linear regression analysis was performed to identify independent predictors of CD4 + T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response. During a follow-up of 24 months, the SVR group showed a mean annual increase in CD4 + T cell from baseline of 84 cells/ll at 1 year and of a further 38 cells/ll within the second year (P=0.01, 0.001, resp.). An insignificant mean increase of 77 cells/ll occurred in the non-SVR group within month 24 (P=0.06). Variables associated with greater CD4 gains were higher nadir, lower preinterferon CD4 counts, and lower body mass index (BMI).


1999 ◽  
Vol 96 (26) ◽  
pp. 15167-15172 ◽  
Author(s):  
N. M. Ferguson ◽  
F. deWolf ◽  
A. C. Ghani ◽  
C. Fraser ◽  
C. A. Donnelly ◽  
...  

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.


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