Divergent hepatitis B neutralizing antibody trajectories after spontaneous control in people with and without HIV

People with HIV (PWH) have reduced spontaneous control (SC) of acute hepatitis B virus (HBV) infection and increased risk of HBV reactivation, but whether protective antibodies against hepatitis B surface antigen (anti-HBs) remain functional after SC is unclear. We analyzed longitudinal antibody responses of 136 men in the MACS/WIHS Combined Cohort Study with incident HBV followed by SC (99 people without HIV [PWoH], 37 PWH) at the first visit consistent with SC and approximately 6 and 30 months later. Anti HBs titers increased over 2.5 years after SC in PWoH but not PWH. Similarly, HBV neutralization was higher after SC in PWoH and remained stable, while trending downward in PWH. In contrast, antibodies against core antigen declined similarly in both groups. Unexpectedly, hepatitis B surface antigen–anti-HBs immune complexes (HBsAg ICs) were present in the majority of samples and remained stable over time. These findings support persistent HBsAg production after SC, which leads to increasing functional anti-HBs control in PWoH that is impaired by HIV potentially explaining effects of HIV on recovery and reactivation risk.