T cell immunity predicts clinical outcomes on stopping antiretroviral treatment after HIV-specific broadly neutralising antibody therapy

There is no readily accessible, scalable cure for HIV infection. Trials of HIV-specific broadly neutralising antibodies (bNAbs) demonstrate inhibition of viral replication and reduction of the reservoir of latently-infected cells, potentially offering new strategies for HIV eradication. Animal and human studies suggest bNAbs have multiple activities, including a direct antiviral action and a secondary induction of T cell responses, the vaccinal effect. The RIO trial assessed HIV-specific cell-mediated immunity after dosing with two long-acting bNAbs (10-1074-LS and 3BNC117-LS) in people treated with antiretroviral therapy (ART) since early stage HIV followed by treatment interruption. BNAbs resulted in sustained viral suppression with 75% of participants controlling off ART after 20 weeks. Here we show that HIV-specific T cell immunity was enhanced for at least 36 weeks after bNAbs in aviraemic participants. Gag-specific T cell immune responses predicted virological outcomes. Baseline CD8+ AIM responses predicted longer times to rebound; baseline CD8+ proliferative responses were additionally protective in participants without baseline bNAb resistance mutations. Baseline ELISpot responses were associated with faster rebound. These data highlight the complex interplay between bNAbs and T cells, identify a post-bNAb protective T cell-driven vaccinal effect, and reinforce the role of immune-based interventions as part of HIV cure strategies.