Increased Thymic Output after Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus Type 1–Infected Children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 Trial

Abstract

To investigate the thymic contribution to immune reconstitution during antiretroviral therapy (ART), T cell receptor gene rearrangement excision circles (TRECs) were measured in peripheral blood mononuclear cells (PBMC) and CD4 cells from 33 human immunodeficiency virus (HIV) type 1-infected children monitored for 96 weeks after ART initiation. Baseline TREC levels were associated positively with baseline CD4 cell percentage and inversely with age and HIV-1 RNA load. During therapy, TREC level changes in PBMC and CD4 cells were fairly comparable. TREC level changes were inversely related to baseline CD4 cell percentage and positively associated with CD4 cell percentage increases, the main source being naive CD4 cells. TREC changes were independent of age and baseline HIV-1 RNA load; however, HIV-1 suppression was independently associated with smaller TREC changes. Thymic output appears to be the main source of CD4 cell repopulation in children receiving ART. Recovery of thymic function is independent of age and influenced by the status of peripheral CD4 cell depletion and HIV-1 suppression.

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

“…In HAART-treated children, immune repopulation may occur despite persistent viraemia [15,16,[19][20][21][22]. To add to the scarce information available on immune reconstitution in HIV-1-infected children, we investigated peripheral immune repopulation in children with and without a virological response to therapy.…”

“…TREC levels were analysed by real-time polymerase chain reaction (PCR), exactly as described previously [15,16].…”

“…+ T cells [13,14], in children immune repopulation involves mainly naive cells, due probably to more efficient thymopoiesis [15][16][17][18]. Furthermore, some children show a discordant response to HAART characterized by a significant increase in CD4 + T cell counts, despite persistent detectable viraemia [15,16,[19][20][21][22].…”

“…Furthermore, some children show a discordant response to HAART characterized by a significant increase in CD4 + T cell counts, despite persistent detectable viraemia [15,16,[19][20][21][22]. Although the mechanisms of this discordant response to HAART have not been elucidated fully, it has been suggested that thymic output [15,16,19,23] and an impaired replicative capacity of drug-resistant viruses [20,24,25] might be involved.…”

CD31 Expression on CD4+ Cells: A Simple Method for Quantitation of Recent Thymus Emigrant CD4 Cells

“…As combined antiretroviral therapy (cART) has become more widely available, it has become clear that while a majority of patients on cART have reduction in viral load, recover, and maintain improved immune capacities, a subset either fails to rapidly recover or maintain robust T-cell capacities. [1][2][3] Direct evidence for thymus failure in these patients can be provided through measurements of naive T-cells that have recently emigrated from the thymus (recent thymus emigrant [RTE]). The reference procedure for measuring RTE cells is quantitation in peripheral blood mononuclear cells of T-cell receptor excision circles (TRECs).…”