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.
Authors
- Nicola Robinson (ORCID: https://orcid.org/0000-0001-5256-4527)
- Panagiota Zacharopoulou (ORCID: https://orcid.org/0000-0002-3645-662X)
- Louise Terry (ORCID: https://orcid.org/0000-0002-8383-657X)
- Whitlock Gary
- Katie Topping
- Graham P. Taylor (ORCID: https://orcid.org/0000-0002-3773-2390)
- Mohammed Altaf (ORCID: https://orcid.org/0000-0001-6977-781X)
- Jesper Damsgaard Gunst (ORCID: https://orcid.org/0000-0002-3787-0259)
- Timothy Tipoe (ORCID: https://orcid.org/0000-0001-5767-9665)
- Rebecca Sutherland (ORCID: https://orcid.org/0000-0001-5214-9630)
- Louise-Rae Cherrill
- Kyle Ring (ORCID: https://orcid.org/0000-0003-4016-4643)
- Sarah Pett (ORCID: https://orcid.org/0000-0002-1882-509X)
- Julia E. Edgar
- Sabine Kinloch
- H. F. Brown
- Frater John
- Devinder Srai
- Emanuela Falaschetti
- Marina Caskey
- Alison J. Uriel
- Carla Nel
- Simon Collins
- Julie Fox
- Stephen Fletcher
- Kelly Seaton
- Ole Sogaard
- Tsmara Elliott
- Marta Boffito
- Philip Goulder
- Ming Lee
- Chance Knight
- Maathini Balachandran
- Chloe Orkin
- Gabriella Lindegard
- Ane Ogbe
- RIO Trial Investigators
- Amanda Clarke
- Hanna Box
- Sarah Fidler
- Georgia Tomaras
Institutions
- NHS Lothian (GB)
- Howard Hughes Medical Institute (US)
- Queen Mary University of London (GB)
- Duke University (US)
- Chinese University of Hong Kong (HK)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Central and North West London NHS Foundation Trust (GB)
- Barts Health NHS Trust (GB)
- Western General Hospital (GB)
- The Royal Free Hospital (GB)
- Aarhus University Hospital (DK)
- University of Oxford (GB)
- Manchester University NHS Foundation Trust (GB)
- NIHR Imperial Biomedical Research Centre (GB)
- Chelsea and Westminster Hospital (GB)
- Oxford BioMedica (United Kingdom) (GB)
- University Hospitals Sussex NHS Foundation Trust (GB)
- University College London (GB)
- Imperial College London (GB)
- Rockefeller University (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-02-03
- DOI
- https://doi.org/10.64898/2026.02.02.26345374
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation
- National Institute for Health and Care Research
- National Institutes of Health
- Center for AIDS Research, University of Washington
- Medical Research Council
- NIHR Imperial Biomedical Research Centre
- NIHR Oxford Biomedical Research Centre