Background: This study aimed at the characterization of cellular immune responses in HIV-infected children and adolescents.

Methods:  3 populations of HIV-infected children and adolescents were studied: Patients with viral suppression on medications (undetectable) for >6 months (n=24, median HIV-1 RNA=40); patients with poorly controlled disease on therapy (viremic) for >6 months (n=15, median HIV-1 RNA=91,000), and patients with stable viral load and CD4 counts (stable) for >6 months either on adequate or inadequate treatment (n=7, median HIV-1 RNA=6200). HIV-1 RNA, CD4 count, CD4%, HIV-specific CD4+ lymphoproliferative (LPA) responses (p24), HIV-specific CD8+ responses (Gag/Env/Pol) qualified by ELISPOT and phenotypic characterization of the T-cell, dendritic and monocyte compartment by flow cytometry were assessed per each patient. Statistics were performed with JMP 4.

Results: LPA responses (p24), and CD4% were significantly higher in the undetectable (p=0.0011 and 0.0004, respectively) and the stable group (p=0.0188 and 0.05, respectively) compared to the viremic, while CD4 count was significantly higher only in the undetectable group compared to the viremic (p=0.0329). Naïve T-cell and dendritic phenotypes followed the same pattern. In contrast to CD4+ T-cell activity, total CD8⁺ T-cell activity was significantly lower in the undetectable group compared to the viremic (p=0.0488). This pattern was also followed by markers of T-cell memory, T-cell and monocyte activation. Regression analysis showed a positive association of LPA responses (p24) to CD4 count and CD4% (n=46, p=0.0021, p=0.0184 respectively), which was also observed in dendritic and naïve T-cell phenotype markers. There was negative association between total CD8+ activity and CD4% (n=32, p=0.0130) as well as memory, T-cell and monocyte activation markers to CD4%. Both CD4 count and CD4% were negatively associated to HIV-1 RNA (n=46, p=0.003, p=0.0026, respectively) and log HIV-1 RNA (n=46, p=0.006, p=0.0002), while only logHIV-1 RNA was negatively associated to LPA responses (p24) (n=47, p=0.0033). Markers of naïve T-cell phenotype were negatively associated, while markers of memory, T-cell and monocyte activation were positively associated to HIV-1 RNA and log HIV-1 RNA

Conclusions: Anti-HIV CD4 T-cell responses are positively associated, while anti-HIV T-cell responses are negatively associated with CD4 count in viral suppressed subjects, where T-cell and monocyte activation is decreased.