HIV Cure Research: Broadly Neutralizing Antibodies Show Promise in Prolonging Remission

New data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2026 suggest that broadly neutralizing antibodies (bNAbs) may significantly alter the dynamics of viral rebound following treatment interruption in individuals living with HIV. Although not a cure, these findings offer early evidence that immune-based interventions could play a role in controlling the virus after stopping antiretroviral therapy (ART).

What are Broadly Neutralizing Antibodies?

Broadly neutralizing antibodies (bNAbs) are antibodies that can neutralize a wide range of HIV strains. They work by binding to conserved regions of the HIV envelope, effectively blocking the virus from entering cells. Some bNAbs are being studied in clinical trials as potential treatments and preventative measures against HIV infection, and to eliminate HIV-infected CD4+ T cells in latent reservoirs.

The RIO Trial: A Two-Phase Approach

The RIO trial is investigating whether bNAbs can maintain undetectable viral loads without the need for ongoing ART. The trial has been conducted in two phases:

RIO A: Initial Findings

The first phase of the RIO trial randomized 68 participants on stable ART to receive either two bNAbs (teropavimab [3BNC117-LS] and zinlirvimab [10-1074-LS]) or a placebo. Participants then stopped their ART in an analytical treatment interruption (ATI). Results showed that 65% of those receiving bNAbs had not reached the criteria for restarting ART by week 20, compared to only 2% in the placebo group. Notably, one participant has remained undetectable off ART for over four years. This trial was recognized as one of the most significant clinical trials of last year by Nature Medicine.

RIO B: Exploring Immunological Effects

The second phase of the trial involved the 34 participants who initially received a placebo. They were then given the two bNAbs while continuing ART, followed by an ATI approximately 24 weeks after the second bNab dose. This delay was intentional, designed to minimize any direct antiviral effect from the bNAbs themselves and to assess whether they induced immunological changes that could contribute to viral control – a “vaccinal effect,” as described by Professor John Frater of the University of Oxford.

In RIO B, 46% of participants did not experience viral rebound within 20 weeks of stopping ART. Six participants had not rebounded by week 39, and five maintained viral loads below or around 1000 for a year. Two participants are still off ART, with one maintaining a completely undetectable viral load for the entire year.

Viral Rebound Dynamics

While the percentage of participants achieving prolonged remission in RIO B (46%) was slightly lower than in RIO A (65%), researchers emphasize the difference in study design. In RIO A, participants stopped ART shortly after receiving bNAbs, allowing for some direct viral suppression. In RIO B, the ATI occurred almost six months after bNab administration, focusing the assessment on potential immunological effects.

Peak viral loads in RIO B were comparable to those in RIO A for those who rebounded quickly. Still, the peak viral loads were significantly lower – around 7000 copies/mL – in those who experienced delayed rebound, compared to approximately 100,000 copies/mL in the initial trial.

Future Directions: RIO C

A third phase of the RIO trial (RIO C) is now underway. This phase will involve participants undergoing two ATIs with periods of ART in between. They will then receive the two bNAbs followed by another period on ART before a third ATI. The goal is to investigate whether periods of viremia can “re-sensitize” the immune system to HIV, potentially generating a stronger T-cell response and further delaying viral rebound.

Key Takeaways

• Broadly neutralizing antibodies show promise in altering viral rebound dynamics after ART interruption.
• The RIO trial demonstrates that bNAbs can prolong remission in some individuals living with HIV.
• Delayed viral rebound and lower peak viral loads were observed in participants receiving bNAbs.
• Further research is needed to understand the immunological mechanisms underlying these effects and to explore the potential for achieving long-term HIV control.