Systemic DPP4/CD26 is associated with natural HIV-1 control: Implications for COVID-19 susceptibility

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals. Flow cytometry was performed to compare cell surface expression of DPP4/CD26 and activation markers on peripheral blood mononuclear cells of extreme clinical phenotypes. Progressors had lower specific DPP4 activity and lower frequency of CD3⁺ T-cells expressing CD26 than HIV-1 controllers, but more activated CD3⁺CD26⁺ T-cells. The frequency of CD26-expressing T-cells negatively correlated with HLA-DR⁺ and CD38⁺ T-cells. Divergent DPP4/CD26 expression between HIV-1 controllers and progressors may have implications for risk and treatment of COVID-19 in people living with HIV.