Biological Aging and Immune Senescence in Children with Perinatally Acquired HIV

Figure 1

Schematic representation of the impact of HIV without (left side, red) and with (right side, blue) ART. HIV infects primarily CD4 cells, and without ART, there is a severe CD4 cell depletion. Microbial translocation from the damaged mucosa, releasing PAMPs (bacterial LPS, 16S rDNA, and CpG DNA) and DAMPs (mtDNA, HMGB1 protein, and defensins), stimulates the production of proinflammatory cytokines (IL-1, IL-6, IL-10, INF-α, and TNF-α) that promote the activation/inflammatory status, a critical hallmark of HIV infection. Immunodeficiency leads to AIDS-related diseases, including AIDS-defining malignancies. With ART, a small fraction of the virus escapes control and establishes the residual reservoir, which promotes a state of chronic low-grade inflammation/activation, where T and B cell phenotype is altered, with increased expression of senescence markers. Accelerated telomere shortening promotes premature aging and may induce genetic instability. This scenario leads to the development of aging-related illnesses, including non-AIDS-defining malignancies.