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

@article{lee2026time,
  title = {{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}},
  author = {Ming Lee and Louise-Rae Cherrill and Panagiota Zacharopoulou and Simon Collins and Marcílio Jorge Fumagalli and Emanuela Falaschetti and Mohammed Altaf and Timothy Tipoe and Piyumika Godakandaarachi and Julie Fox and Alison Uriel and Amanda E. Clarke and Sabine Kinloch‐de Loes and Sarah Lilian Pett and Marta Boffito and Gary George Whitlock and Ole Schmeltz Søgaard and Kyle Ring and Irvine Mangawa and Jesal Gohil and Tamara Elliott and Henrik Nielsen and Jesper Damsgaard Gunst and Chloe M. Orkin and Rebecca Sutherland and Lisa Hamzah and Paola Cicconi and Graham Philip Taylor and Jacquie Ujetz and Ishrat Jahan and Helen Brown and Nicola Robinson and Stephen Fletcher and Hanna Box and Kelly E. Seaton and Georgia D. Tomaras and Margaret E. Ackerman and Joshua A. Weiner and Anna Kaczynska and Cíntia Bittar and Jill A. Horowitz and Michel C. Nussenzweig and Marina F. Caskey and John Frater and Sarah J. Fidler},
  journal = {The Lancet HIV},
  year = {2026},
  month = may,
  doi = {10.1016/s2352-3018(26)00059-7},
  url = {https://doi.org/10.1016/s2352-3018(26)00059-7},
  note = {CC BY},
}

TY  - JOUR
TI  - 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
AU  - Ming Lee
AU  - Louise-Rae Cherrill
AU  - Panagiota Zacharopoulou
AU  - Simon Collins
AU  - Marcílio Jorge Fumagalli
AU  - Emanuela Falaschetti
AU  - Mohammed Altaf
AU  - Timothy Tipoe
AU  - Piyumika Godakandaarachi
AU  - Julie Fox
AU  - Alison Uriel
AU  - Amanda E. Clarke
AU  - Sabine Kinloch‐de Loes
AU  - Sarah Lilian Pett
AU  - Marta Boffito
AU  - Gary George Whitlock
AU  - Ole Schmeltz Søgaard
AU  - Kyle Ring
AU  - Irvine Mangawa
AU  - Jesal Gohil
AU  - Tamara Elliott
AU  - Henrik Nielsen
AU  - Jesper Damsgaard Gunst
AU  - Chloe M. Orkin
AU  - Rebecca Sutherland
AU  - Lisa Hamzah
AU  - Paola Cicconi
AU  - Graham Philip Taylor
AU  - Jacquie Ujetz
AU  - Ishrat Jahan
AU  - Helen Brown
AU  - Nicola Robinson
AU  - Stephen Fletcher
AU  - Hanna Box
AU  - Kelly E. Seaton
AU  - Georgia D. Tomaras
AU  - Margaret E. Ackerman
AU  - Joshua A. Weiner
AU  - Anna Kaczynska
AU  - Cíntia Bittar
AU  - Jill A. Horowitz
AU  - Michel C. Nussenzweig
AU  - Marina F. Caskey
AU  - John Frater
AU  - Sarah J. Fidler
PY  - 2026
DA  - 2026/05/27
JO  - The Lancet HIV
DO  - 10.1016/s2352-3018(26)00059-7
UR  - https://doi.org/10.1016/s2352-3018(26)00059-7
AB  - 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.
SN  - 2352-3018
SN  - 2405-4704
ER  -