Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment

Background: Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. Methods: Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. Results: HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4(+) T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4(+) T cells and heightened HLA-DR and T-bet in CD8(+) T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR(+)CD4(+), Ki67(+)CD4(+), PD-1(+)CD4(+), CD38(+)CD8(+), HLA-DR(+)CD8(+), TIM-3(+)CD8(+), HBV-specific CD4(+) T cell secreting IFN-gamma and IL-2, and specific CD8(+) T cell secreting IFN-gamma and IL-2, correlated with HBsAg decrease. Conclusion: The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4(+) and CD8(+) T cells phenotypes, offering a novel perspective on a functional HBV cure.