Background:  Little is known of the state of innate and adaptive immunity in HIV-infected children not on ART in relation to disease stage and disease progression.

Methods:  A prospective study of 62 perinatally HIV-infected children naïve to ART, age range 3 to 13 years, median plasma virus load 91,300 HIV RNA copies/mm³ (range 4490 to 75,000) was conducted in Chennai, India, to investigate phenotypic markers of T cells and phenotype/functions of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) by flow cytometry. Patients were classified into immune category (IC-1) (CD4% >25, n = 20, 32.5%), IC-2 (CD4% 15 to 25, n = 20, 53.5%) and IC-3(CD4% <15, n = 9, 14%). Median age was similar (6 to 7 years) in the 3 groups. We included 8 age-matched healthy controls. Results were analyzed by analysis of variance.

Results:  Among the 3 groups, patients in IC-3 manifested significantly lower proportion of naïve (CD45RA⁺CD62L⁺) CD4 and CD8 T cells as compared to IC-1, IC-2, and controls (p = ≤0.002 for all), with expansion of activated (CD38⁺HLA-DR⁺) CD4 and CD8 T cells (p <0.05), CD8 T cells manifested higher activation than CD4 (p = 0.022). Central memory (CD45RA^–CD62L⁺) population was expanded in the IC-3 subgroup as compared to IC-1 in CD4 (p = 0.008) and CD8 (p = 0.045) T subsets. Expansion was also evident in proportions of pDC and mDC in patients in IC-3, as compared to IC-1 (p = 0.008 and p = 0.034, respectively). Upon stimulation with Toll-like receptor (TLR) -7/8 agonist resiquimod (RSQ), up-regulation of maturation marker (CD83) was less in IC-3 compared to healthy controls in mDC (p = 0.05) and pDC (p <0.001). RSQ induced up-regulation of CD80 and CCR7 was equivalent in mDC and pDC in all patient groups in comparison with controls. RSQ-induced cytokines, interferon-alpha (IFN-a) in pDC and tumor necrosis factor-alpha (TNF-a) in mDC and pDC were equivalent in all patient groups and controls. Over a 9-month follow-up, 9 patients were started on ART and rapidly normalized CD4 T cells, with virologic suppression to undetectable levels in 5 of 9; those not on therapy remained stable. 

Conclusions:  This cohort of HIV-infected children manifested strong mDC and pDC numbers and function, and only subjects in IC-3 manifested an isolated defect in stimulus-induced up-regulation of maturation marker, CD83. Depletion of naïve CD4 T cells and increased immune activation remained the most predictable markers of disease progression. Intact DC function may contribute to disease stability in this group of older HIV-infected children.