NK cell dysregulation may potentiate cardiovascular disease in adolescents with perinatally acquired HIV on antiretroviral therapy.

Perinatally acquired HIV (PHIV) and antiretroviral therapy (ART) can alter innate immune cells, (monocytes and natural killer [NK] cells) which are important in the pathogenesis of cardiovascular disease (CVD). We compare cardiovascular biomarkers and immune signatures between adolescents with PHIV (APHIV) on suppressive ART and HIV-unexposed, adolescents without HIV in Uganda. Carotid intima-media thickness (IMT) is increased in APHIV, suggesting a higher CVD risk. Flow cytometry analysis reveals greater activation, memory, and migratory capabilities of NK cells, and increased pro-inflammatory intermediate monocytes in APHIV, and these observations are supported by transcriptomics. Many of these innate immune cell subsets are associated with carotid IMT. Plasma oxidized-LDL (Ox-LDL) is significantly lower among APHIV, and negatively correlates with pro-inflammatory, memory-like NK subsets. We demonstrate increased uptake of Ox-LDL by macrophages in the presence of activated, memory-like NK cells in vitro, suggesting a possible mechanism for greater CVD risk in APHIV. Collectively, our data demonstrate associations between dysregulated NK cell signatures and increased CVD risk among APHIV.