People living with HIV have increased CD4+ T cell metabolic activity and reduced influenza-reactive cellular responses to vaccination 2260148

Introduction While antiretroviral therapy has improved health outcomes for people living with HIV (PLWH), individuals are more likely to experience severe influenza infection and infection-related complications. Methods This study investigated basal immunometabolic function and influenza vaccine-induced antibody and T cell responses in 17 PLWH on antiretroviral therapy and 17 individuals living without HIV (PLWoH). Results We found no significant differences in serum hemagglutination inhibition antibody titers against influenza A (H1N1, H3N2) or influenza B (B-Victoria, B-Yamagata) antigens between PLWH and PLWoH pre- and post-vaccination, nor in the fold-change of titers. Only PLWoH had significantly increased frequencies of influenza-reactive CD4+ T cells in response to influenza vaccination. Naive and memory CD4+ T cells from PLWH exhibited higher basal metabolic activity compared to PLWoH. CD4+ T cell activation and metabolic activity in PLWH were largely independent of HIV viral load. Conclusion These findings suggest that while PLWH can mount humoral responses to influenza vaccination, increased CD4+ T cell activation and altered metabolism of CD4+ T cells may influence cellular immune responses to vaccination. This highlights how the adaptive immune system in PLWH is affected even when HIV replication is controlled.