Relationship between Changes in Thymic Emigrants and Cell-Associated HIV-1 Dna in HIV-1-Infected Children Initiating Antiretroviral Therapy
De Rossi A., Walker AS., Forni DD., Klein N., Gibb DM., Aboulker J-P., Babiker A., Compagnucci A., Darbyshire J., Debré M., Gersten M., Giaquinto C., Gibb DM., Jones A., Aboulker J-P., Babiker A., Blanche S., Bohlin A-B., Butler K., Castelli-Gattinara G., Clayden P., Darbyshire J., Debré M., de Groot R., Faye A., Giaquinto C., Gibb DM., Griscelli C., Grosch-Wörner I., Levy J., Lyall H., Mellado Pena M., Nadal D., Peckham C., Ramos Amador JT., Rosado L., Rudin C., Scherpbier H., Sharland M., Tovo PA., Valerius N., Wintergerst U., Boucher C., Clerici M., de Rossi A., Klein N., Loveday C., Muñoz-Fernandez M., Pillay D., Rouzioux C., Babiker A., Darbyshire J., Gibb DM., Harper L., Johnson D., Kelleher P., McGee L., Poland A., Walker AS., Aboulker J-P., Carrière I., Compagnucci A., Debré M., Eliette V., Leonardo S., Moulinier C., Saidi Y., Galli L., Foot A., Kershaw H., Caul O., Tarnow-Mordi W., Petrie J., McIntyre P., Appleyard K., Gibb DM., Novelli V., Klein N., McGee L., Ewen S., Johnson M., Gibb DM., Cooper E., Fisher T., Barrie R., Norman J., King D., Larsson-Sciard E-L.
Objectives and methods To 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. Results At 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. Conclusions Overall, 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.