Dengue-specific T-cell memory following natural infection: a comparative analysis between people living with HIV and HIV-negative individuals

People living with HIV (PLWH) represent a population of particular interest in the context of arboviral infections. This observational study aimed to evaluate and compare the magnitude and functionality of dengue virus (DENV)-specific T-cell memory elicited by natural DENV infection in PLWH and HIV-negative individuals. Nineteen participants infected during the 2023 autochthonous dengue outbreak in Rome (10 PLWH and 9 HIV-negative individuals) were assessed for interferon gamma (IFN-gamma)-releasing cells in peripheral blood mononuclear cells (PBMCs) using an IFN-gamma -ELISpot assay following stimulation with peptide pools.When examining both the overall cumulative ELISpot responses, calculated as the sum of spot-forming units (SFU) across all antigens or the binary responder status to each DENV antigen, HIV-negative individuals showed higher and broader cumulative responses than PLWH, but differences did not reach statistical significance. However, responses to prM/E/C antigens were higher in the HIV-negative group, reaching statistical significance (P = 0.041). Among PLWH, no association was found between T-cell reactivity and CDC stage at diagnosis. Our findings suggest that while PLWH with well-controlled infection retain dengue-specific T-cell memory, their response to structural antigens may be attenuated. Vaccination should be considered a key preventive strategy for this clinically vulnerable population.IMPORTANCEThe geographic expansion of dengue virus (DENV) transmission into temperate regions highlights the need to characterize immune responses in populations with chronic conditions such as HIV. Despite immune reconstitution under antiretroviral therapy (ART), people living with HIV (PLWH) may exhibit residual immune dysregulation that could affect DENV-specific immunity and clinical outcomes. In this study, we directly compared DENV-specific T-cell memory responses in PLWH and HIV-negative individuals following natural infection during an autochthonous outbreak. While PLWH mounted detectable cellular responses, reactivity to structural antigens (prM/E/C) was significantly reduced compared with HIV-negative participants. These findings indicate that qualitative differences in antigen-specific T-cell memory may persist despite virological suppression and immune recovery, with potential implications for protection upon re-exposure. Our results provide a rationale for evaluating dengue vaccination strategies in PLWH as local transmission becomes more frequent in non-endemic settings.The geographic expansion of dengue virus (DENV) transmission into temperate regions highlights the need to characterize immune responses in populations with chronic conditions such as HIV. Despite immune reconstitution under antiretroviral therapy (ART), people living with HIV (PLWH) may exhibit residual immune dysregulation that could affect DENV-specific immunity and clinical outcomes. In this study, we directly compared DENV-specific T-cell memory responses in PLWH and HIV-negative individuals following natural infection during an autochthonous outbreak. While PLWH mounted detectable cellular responses, reactivity to structural antigens (prM/E/C) was significantly reduced compared with HIV-negative participants. These findings indicate that qualitative differences in antigen-specific T-cell memory may persist despite virological suppression and immune recovery, with potential implications for protection upon re-exposure. Our results provide a rationale for evaluating dengue vaccination strategies in PLWH as local transmission becomes more frequent in non-endemic settings.