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

Abstract: Immune repopulation, despite virological failure, often occurs in children under highly active anti-retroviral therapy (HAART). The aim of this study was to analyse the characteristics of immune repopulation and activation in children with and without virological response to HAART. Fourteen human immunodeficiency virus type 1 (HIV-1)-infected children with suppression of HIV-1 plasma viraemia (virological responders, VR) and 16 virological non-responders (VNR) to therapy were studied at baseline and after approximately 2 years of HAART. During therapy, CD4(+) T cells increased in both groups, but were higher in the VR than in the VNR group. All CD4(+) T cell subsets (naive, central memory, effector/memory and CD38(+)) increased significantly in VR children, while there was a significant increase only in naive cells in VNR children. Naive CD8(+) T cells and T cell receptor rearrangement excision circles (TREC), an indicator of thymic output, increased in both VR and VNR children. Activated CD8(+)CD38(+) T cells decreased in VR but remained high in VNR children. Levels of circulating lipopolysaccharide (LPS), an indicator of microbial translocation, further increased in VNR children. In conclusion, HAART induced an increase in naive cells in all children, regardless of their virological response. However, the persistence of viraemia resulted in an impaired expansion of memory CD4(+) T cells susceptible to HIV-1 infection, and together with the microbial translocation sustained the persistence of a high level of immune activation