In vitro NAD + supplementation increases CD4 + and CD8 + T cell function in people with HIV

OBJECTIVES: HIV perturbs T cell homeostasis and disrupts immune function, increasing the risk of age-associated comorbidities. Ageing people with HIV (PWH) have exacerbated expression of CD38 on T cells, which depletes intracellular nicotinamide adenine dinucleotide (NAD+). We investigated whether boosting intracellular NAD+ could restore T cell homeostasis and function. METHODS: We collected blood samples from virally suppressed PWH to determine the effects of in vitro NAD+ on CD38 expression and T cell function in response to anti-CD3/CD28 antibodies stimulation in PBMCs culture supplemented with IL-2 and IL-7. RESULTS: We observed that NAD+ supplementation not only reduced expression of CD38 but also improved T cell function with an alleviated exhaustion phenotype in response to anti-CD3/CD28 antibodies stimulation. CONCLUSIONS: If confirmed in clinical trials, NAD+ supplementation has the potential to restore T cell homeostasis and immune function in PWH and ameliorate age-associated comorbidities.