Relationship between Changes in Thymic Emigrants and Cell-Associated HIV-1 Dna in HIV-1-Infected Children Initiating Antiretroviral Therapy

Abstract

Objectives and methodsTo investigate the relationship between cell-associated HIV-1 dynamics and recent thymic T-cell emigrants, HIV-1 DNA and T-cell receptor rearrangement excision circles (TREC, a marker of recent thymic emigrants) were measured in peripheral blood mononuclear cells in 181 samples from 33 HIV-1-infected children followed for 96 weeks after antiretroviral therapy (ART) initiation.ResultsAt baseline, HIV-1 DNA was higher in children with higher TREC ( P=0.02) and was not related to age, CD4 or HIV-1 RNA in multivariate analyses ( P>0.3). Overall, TREC increased and HIV-1 DNA decreased significantly after ART initiation, with faster HIV-1 DNA declines in children with higher baseline TREC ( P=0.009). The greatest decreases in HIV-1 DNA occurred in children with the smallest increases in TREC levels during ART ( P=0.002). However, this inverse relationship between changes in HIV-1 DNA and TREC tended to vary according to the phase of HIV-1 RNA decline ( P=0.13); for the same increase in TREC, HIV-1 DNA decline was much smaller during persistent or transient viraemia compared with stable HIV-1 RNA suppression.ConclusionsOverall, these findings indicate that TREC levels predict HIV-1 DNA response to ART and suggest that immune repopulation by thymic emigrants adversely affects HIV-1 DNA decline in the absence of persistent viral suppression, possibly by providing a cellular source for viral infection and replication.