Associations between recent thymic emigrants and CD4+ T-cell recovery after short-term antiretroviral therapy initiation

Objective: Around 20-30% of HIV-infected individuals (HIV+) on successful antiretroviral therapy (ART) fail to normalize their CD4(+) T-cell counts. Various factors could contribute to the lack of immune reconstitution, one of them being thymic insufficiency. We aimed to explore associations between recent thymic emigrants (RTEs) and CD4(+) T-cell recovery. Design: ART-naive HIV+ individuals who started ART with advanced AIDS were selected. Good versus poor immune reconstitution was defined by CD4(+) gains above or below 100 CD4(+) T cells/mu l. The follow-up period was 6 months. Methods: Peripheral blood mononuclear cells were isolated and flow cytometry was used to characterize RTEs as the fraction of naive CD4(+) T cells expressing CD31(+), the platelet endothelial cell adhesion molecule. Markers of cellular activation, senescence, exhaustion and cycling were also assessed. Results: After 6 months on ART, HIV+ individuals with good immune reconstitution had higher absolute numbers of RTEs, compared with those with poor immune reconstitution, and these strongly correlated with CD4(+) gains in those individuals with good immune reconstitution but not with poor immune reconstitution. We also found that CD8(+) T-cell immune activation decreased as early as 2 months post-ART initiation in individuals with good immune reconstitution, but only at month 6 post-ART in individuals with poor immune reconstitution. Levels of immune activation were inversely correlated with the absolute numbers of RTEs in both groups, but more strongly so in individuals with poor immune reconstitution. Conclusion: We show that RTEs are linked to CD4(+) T-cell recovery and that the degree of immune reconstitution is not directly linked to persistent immune activation.