How past transient viremia shape natural killer cells’ antibody-dependent functions in youth with perinatal HIV

Despite effective antiretroviral therapy, people living with HIV (PLWH) may experience transient viremia episodes, which may impact Natural Killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC). This study aimed to assess ADCC in youth with perinatal HIV compared with healthy controls (HC) and in relation to prior viremia. 22 PLWH were stratified by virological history and assessed during viral suppression. Peripheral blood mononuclear cells were stimulated with HIV + 8E5LAV cells with autologous or heterologous HIV plasma to assess ADCC by multicolor flow cytometry. PLWH showed reduced ADCC compared with HC. PLWH with multiple prior viremia episodes showed increased antibody-dependent NK degranulation and a trend toward higher IFN-γ production upon autologous plasma stimulation, without impaired intrinsic NK ADCC capability in response to heterologous plasma. These findings suggest that transient exposure to autologous virus may enhance ADCC in PLWH, supporting further investigation of its potential relevance for HIV remission strategies in larger independent cohorts.