Lewis, J;
Payne, H;
Walker, AS;
Otwombe, K;
Gibb, DM;
Babiker, AG;
Panchia, R;
... Callard, RE; + view all
(2017)
Thymic output and CD4 T-cell reconstitution in HIV-infected children on early and interrupted antiretroviral treatment: evidence from the CHER trial.
Frontiers in Immunology
, 8
, Article 1162. 10.3389/fimmu.2017.01162.
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Abstract
OBJECTIVES: Early treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants’ immune systems are more plastic and dynamic than older children’s or adults’, and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART) and planned ART interruption and re-start. DESIGN: We used linear and nonlinear regression and mixed-effects models to describe children’s CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART. METHODS: Data from HIV-infected children enrolled CHER trial, starting ART aged between 6 and 12 weeks, was used to explore the effect of ART on immune reconstitution. RESULTS: Early treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption. CONCLUSIONS: Early identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children’s CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children’s CD4 levels.
| Type: | Article |
|---|---|
| Title: | Thymic output and CD4 T-cell reconstitution in HIV-infected children on early and interrupted antiretroviral treatment: evidence from the CHER trial |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2017.01162 |
| Publisher version: | http://doi.org/10.3389/fimmu.2017.01162 |
| Language: | English |
| Additional information: | © 2017 Lewis, Payne, Walker, Otwombe, Gibb, Babiker, Panchia, Cotton, Violari, Klein and Callard. 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) or licensor 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. |
| Keywords: | HIV, Children, antiretroviral therapy, planned treatment interruption, CD4 T cells, CD4 count, Thymus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1572260 |
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