2. Academic Validation
  3. Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial

Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial

  • Lancet HIV. 2026 May 27:S2352-3018(26)00059-7. doi: 10.1016/S2352-3018(26)00059-7.
Ming J Lee 1,  Louise-Rae Cherrill 2,  Panagiota Zacharopoulou 3,  Simon Collins 4,  Marcilio Fumagalli 5,  Emanuela Falaschetti 2,  Mohammed Altaf 3,  Timothy Tipoe 6,  Piyumika Godakandaarachi 7,  Julie Fox 7,  Alison Uriel 8,  Amanda Clarke 9,  Sabine Kinloch-de Loes 10,  Sarah Pett 11,  Marta Boffito 12,  Gary Whitlock 12,  Ole S Søgaard 13,  Kyle Ring 14,  Irvine Mangawa 8,  Jesal Gohil 1,  Tamara Elliott 15,  Henrik Nielsen 16,  Jesper Damsgaard Gunst 13,  Chloe Orkin 14,  Rebecca Sutherland 17,  Lisa Hamzah 18,  Paola Cicconi 19,  Graham P Taylor 2,  Jacquie Ujetz 2,  Ishrat Jahan 2,  Helen Brown 3,  Nicola Robinson 3,  Stephen Fletcher 2,  Hanna Box 20,  Kelly E Seaton 21,  Georgia D Tomaras 21,  Margaret E Ackerman 22,  Joshua A Weiner 22,  Anna Kaczynska 5,  Cintia Bittar 5,  Jill Horowitz 5,  Michel C Nussenzweig 23,  Marina Caskey 5,  John Frater 24,  Sarah Fidler 25,  RIO Study Team
Affiliations

Affiliations

  • 1 Department of Infectious Disease, and Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Imperial College Healthcare NHS Trust, London, UK.
  • 2 Department of Infectious Disease, and Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
  • 3 Nuffield Department of Medicine, University of Oxford, London, UK.
  • 4 HIV i-Base, London, UK.
  • 5 The Rockefeller University, New York, NY, USA.
  • 6 Nuffield Department of Medicine, University of Oxford, London, UK; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
  • 7 Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK.
  • 8 Manchester University NHS Foundation Trust, Manchester, UK.
  • 9 University Hospitals Sussex NHS Foundation Trust and Brighton & Sussex Medical School, Brighton, UK.
  • 10 Royal Free London NHS Foundation Trust, London, UK; University College London, London, UK.
  • 11 University College London, London, UK; Central and North West London NHS Foundation Trust, London, UK.
  • 12 Chelsea and Westminster Hospital, London, UK.
  • 13 Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
  • 14 Queen Mary University of London and Barts Health NHS Trust, London, UK.
  • 15 Department of Infectious Disease, and Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Imperial College Healthcare NHS Trust, London, UK; National Institute for Health Research, Imperial Biomedical Research Centre, London, UK.
  • 16 Aalborg University and Aalborg University Hospital, Aalborg, Denmark.
  • 17 Western General Hospital, NHS Lothian Trust, Edinburgh, UK.
  • 18 St George's University Hospitals, NHS Foundation Trust, London, UK.
  • 19 Nuffield Department of Medicine, University of Oxford, London, UK; Centre for Clinical Vaccinology and Tropical Medicine and the Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • 20 Department of Infectious Disease, and Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK; National Institute for Health Research, Imperial Biomedical Research Centre, London, UK.
  • 21 Duke University, Durham, NC, USA.
  • 22 Dartmouth College, Hanover, NH, USA.
  • 23 The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • 24 Nuffield Department of Medicine, University of Oxford, London, UK; National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, UK.
  • 25 Department of Infectious Disease, and Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Imperial College Healthcare NHS Trust, London, UK; National Institute for Health Research, Imperial Biomedical Research Centre, London, UK. Electronic address: [email protected].
PMID: 42202839 DOI: 10.1016/S2352-3018(26)00059-7
Abstract

Background: HIV-specific broadly neutralising antibodies (bNAbs) can maintain viral control after interrupting antiretroviral therapy (ART). We investigated the duration and efficacy of Fc-engineered long-acting bNAbs (LS-bNAbs) in maintaining ART-free HIV control compared with placebo.

Methods: RIO is a double-blind, randomised, placebo-controlled trial. Eligibile participants were adults age 18-60 years, initiated on ART in early-stage HIV Infection, virally suppressed on ART, and had no evidence of viral insensitivity to 10-1074. Participants were randomly assigned (1:1) to receive two LS-bNAbs (3BNC117-LS and 10-1074-LS) in arm A or saline placebo in arm B; participants and study staff were masked to assignment. Eligible participants interrupted ART after receiving blinded intravenous infusions of either bNAbs or placebo. A second optional infusion was offered after 20 weeks for participants who remained virally suppressed without ART. The primary outcome was time to viral rebound 20 weeks after ART interruption, defined as either the first of six consecutive plasma HIV RNA measurements greater than 1000 copies per mL, or two measurements greater than 100 000 copies per mL. All randomly assigned participants were included in the analyses. This study is registered with ClinicalTrials.gov, NCT04319367.

Findings: 68 participants were randomly assigned, 34 to each arm. By week 20, viral rebound had occurred in eight participants in arm A and 30 in arm B; 75% (95% CI 61-92) of participants in arm A did not have viral rebound, compared with 11% (4-29) of participants in arm B. Participants in arm A were 91% less likely to rebound than were those in arm B (hazard ratio 0·09; 95% CI 0·04-0·21, p<0·0001). There were 326 adverse events in arm A and 260 in arm B, including 19 treatment-related or procedure-related adverse events in arm A and 41 in arm B. Of nine serious adverse events, none were treatment-related. The most commonly reported treatment-related or procedure-related adverse events were fatigue, lethargy, or somnolence: 11 in arm A and nine in arm B. There were two severe adverse events (anal abscesses) possibly related to the study protocol, both in the placebo arm.

Interpretation: Long-acting bNAbs can sustain extended ART-free viral control in people treated during early-stage HIV and represent a promising step towards achieving ART-free HIV remission.

Funding: Gates Foundation.

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