Premature aging and immune senescence in HIV-infected children

Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. DESIGN: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0–5 years, were studied for biological aging and immune senescence. METHODS: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4(+) and CD8(+) cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. RESULTS: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8(+) recent thymic emigrant cells (CD45RA(+)CD31(+)) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28(−)CD57(+)), activated (CD38(+)HLA-DR(+)), and exhausted (PD1(+)) CD8(+) cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4(+) cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. CONCLUSIONS: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8(+) cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment.