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
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2026-08-01
Date Acceptance
2026-05-01
Citation
The Lancet HIV, 2026, 13 (8), pp.E527-E537
ISSN
2352-3018
Publisher
Elsevier BV
Start Page
E527
End Page
E537
Journal / Book Title
The Lancet HIV
Volume
13
Issue
8
Copyright Statement
© 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/42202839
PII: S2352-3018(26)00059-7
Subjects
RIO Study Team
Publication Status
Published
Coverage Spatial
Netherlands
Date Publish Online
2026-05-27