Background: HIV-infected children reconstitute multiple lymphocyte lineages following antiretroviral therapy with protease inhibitors (PI). This study is based on the hypothesis that patterns of immune reconstitution differ between children who display a discordant treatment response and those who suppress viral replication.

Methods: A prospective, 48-week study included 40 PI-naïve HIV-infected children with advanced immune suppression and high viral loads pre-therapy. Viral and immune outcomes were determined based on 24-week treatment responses. Subjects either fully suppressed virus (viral success, VS) or showed viral breakthrough (viral failure, VF). Immune success (IS), or failure (IF) outcomes were based on changes in CD4 T cell counts. Median changes from baseline in the number of B cells, CD8 T cells, and CD4 T cell subsets were monitored over 48 weeks of treatment. TCR Vß repertoire was evaluated in CD45RA and CD45RO CD8 subsets using spectratyping. Outcomes within response groups were evaluated by Wilcoxan Rank sum test and among response groups using Kruskal-Wallis analysis of variance.

Results: Outcome groups within the study cohort were VSIS (34%), VFIF (12%), VFIS (41%), and VSIF (9%). Change in CD4 T cell counts within the VSIS and VFIS groups was similar (373 and 478 cells/m, respectively). Naïve, CD4 CD45RA T cells were the predominant subset contributing to the increase in CD4 T cell numbers (239 and 384 cells/ul in VSIS and VFIS). No significant change in CD4 T cell numbers occurred in the VFIF group, but VSIF showed a sustained increase from 24 to 48 weeks (70 to 140 cells/mL). By 24 weeks, both VSIS and VFIS groups demonstrated significant increases in B cell numbers (65 and 208 cells/ul, respectively) but not in the IF groups. CD8 T cells increased in both viral failure groups (289 cells/ul, VFIF and 503 cell/ul VFIS) but decreased in the VS groups (-77 cells/mL VSIS and -9 cells/mL VSIF). TCR Vß perturbations within CD8 CD45RA cells declined in VSIS subjects, but persisted in VFIS. No significant therapy induced differences occurred within the TCR Vß repertoire of CD8 CD45RO T cells. 

Conclusions: Failure to control viral replication with PI leads to significant reconstitution of naïve CD4 T cells and B cells in most children, suggesting emergence of less pathogenic viruses post therapy. CD8 T cells in discordant responses remain activated and show a skewed TCR Vß repertoire in CD8 CD45RA cells.

Keywords: Immune reconstitution; Children; Discordant Response