AIDS 2026: The promise of bNAbs in HIV cure-related research in chronic infection

17 August 2026. Related: Conference reports, Cure-related research, Basic science and immunology, Intl AIDS 26th Rio 2026.

Simon Collins, HIV i-Base

One of the first plenary sessions at AIDS 2026 included an overview of the role of bNAbs in cure-related research. [1]

The talk was given by Michel Nussenzweig from Rockefeller University, whose leading role in this field includes developing 10-1074 and 3BNC117, which are now licensed to Gilead and in development as zinlirvimab (ZAB) and teropavimab (TAB).

In addition to describing the history of this research, the talk reported new data on factors associated with durable viral suppression off ART following bNAb treatment. This included having less viral diversity within the reservoir of latently infected cells and, unexpectedly, no relationship to the overall size of this reservoir.

Until now, most cure-related research has only recruited people who were diagnosed in early infection and who started early ART. These new findings suggest that bNAb research might have benefits in people diagnosed much later, during chronic infection.

bNAbs work in two ways that support their role as a component of an HIV cure. In addition to having direct antiviral activity similar to other HIV drugs, bNAbs also sometimes stimulate a vaccine-like immune response. This continues to suppress viral load long after drug levels have become undetectable or dropped below therapeutic levels.

The talk also included early results from the phase-1 MCA-1031 study, led by Marina Caskey, the clinical lead investigator at the same Rockefeller lab. This study had more open entry criteria, without requiring pre-screening sensitivity tests for the bNAbs and also using an IL-15 agonist called N-803.

So far, five responders have maintained viral suppression for at least 72 weeks ­off ART – including one person now out to three years. Although low-level viral blips were reported, none of these participants reached the restart criteria of two consecutive viral load results >200 copies/mL. The results also included that the rebounding HIV was phylogenetically different at different timepoints. Rebounding virus during the first seven weeks was similar to the reservoir but then disappeared with different viruses from weeks 12 to 34, changing again after week 34. This suggests that the pool of proviral diversity also changes in response to bNAb-induced T-cell activity.

Of note, bNAbs reduced levels of intact proviruses in the viral reservoir but no relation was seen between response rates and the size of the viral reservoir – despite this being an expected outcome. However, greater sensitivity to either 10-1074 and 3BNC117 and stronger autologous immune-responses to a participant’s own virus were associated with longer viral suppression off ART. Other significant correlates included levels of stem-like HIV-specific CD8 T-cells responses that have also been seen in post-treatment controllers.

Although stopping ART generally leads to rapid viral load rebound within 2 to 3 weeks, the RIO study, with study sites primarily in the UK, recently reported that 75% of participants receiving  10-1074 and 3BNC117 were able to safely stay off ART for more than 20 weeks. [2, 3, 4]

Six participants (25%) in the active arm have maintained viral suppression <1000 copies/mL for 96 weeks compared to only two participants with post-treatment control (PCT) responses in the placebo group. Sustained viral suppression for more than two years after stopping ART is one of the elements of the IAS target product profiles for an HIV cure.

Summarising the importance of the new results, Nussenzweig concluded that researchers now know factors that can predict the likelihood of sustained responses to bNAb therapy and that these can be targeted with new interventions that could improve such responses.

Expert overview and Q&A panel

The role of bNAbs and other interventions in cure-related work, including CAR-T therapy were discussed further in an interactive panel discussion and Q&A, introduced and chaired by Professor Sarah Fidler from Imperial College London who is also one of the joint lead-investigators for the RIO study. [5]

The session looked at both advantages and difficulties of bNAbs – the hype and the hope – which are significant, including predicting bNAb sensitivity and potential cost. Most panelists were optimistic that bNAbs showed promise to have a role in a future HIV cure, although they won’t be able to do this alone, but in combination with other treatments.

The practical issues for people maintained off ART during a treatment interruption include the challenges of not yet having a point-of-care viral load test that could be used at home, and the potential risk to sexual partners if and when viral rebound occurs. The discussion partly resolved this by suggesting that no longer being able to rely on U=U for partner protection might be acceptable for many people in exchange for not needing to take ART.

Several presentations referred to the importance of future bNAbs that have greater potency and breadth, and the discussion included a question about how new candidate bNAbs are identified. The answer, which continued in a panel discussion after the session, is that finding new bNAbs is difficult and that these are unfortunately not generally found in either elite controllers or post-treatment controllers, despite their immunological control, but in non-controllers who for some reason haven’t used ART.

The challenge is not just discovering new and better bNAbs, but crossing the bridge from preclinical work to clinical development, as it costs several million dollars just to get to phase 1 testing.

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The extended responses in a sub-group of participants in these small studies are the most convincing proof-of-principle that the immune system can be trained to maintain viral suppression off ART. They also demonstrate proof-of-principle for reducing replication-competent HIV in the viral reservoir. 

Many other aspects of bNAb research included as treatment in infants, children and adults [6], as prophylaxis against vertical transmission [7], and coverage during infant feeding. Also, there were disappointing results from the placebo-controlled, dual bNAb CAPRISA study for HIV prevention in adults, although the in vivo efficacy of CAP256 is unclear and whether the dosing strategy was optimum [8].

Note: Simon Collins is a community representative on the RIO study.

References

1. Nussenzweig M. bNAbs: Where are we and where do we go from here? Plenary talk in Rethink. Rebuild. Rise.
   https://programme.aids2026.org/Programme/Session/3
   https://conference.aids2026.org/media-312-rethink-rebuild-rise (webcast)
2. Lee M et al. 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. 13(8); e527-e537. August 2026.
   https://www.sciencedirect.com/science/article/pii/S2352301826000597
3. Elliot T et al. HIV viral control after bNAb “wash-out” and relationship to HIV viraemia at dosing; preliminary results from the RIO trial. Poster abstract WEPEB127.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=8136
4. Nel C et al. Immunological comparison of viral control in the RIO trial versus HIV elite and post-treatment controllers. AIDS 2026. Poster abstract HPEA011.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=7912
5. bNAbs for cure: hype or hope. Symposium and panel discussion. 28 July 2026.
   https://conference.aids2026.org/media-365-bnabs-for-cure-hope-or-hype
6. McMahon J et al. Efficacy and safety of twice-yearly lenacapavir, teropavimab, and zinlirvimab as an HIV-1 treatment for up to 104 weeks. AIDS 2026, Oral abstract OAB1403.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=9973
7. Kroidl A et al. Genetic diversity and predicted broadly neutralizing antibody coverage of vertically transmitted HIV-1 subtype C in Mozambican children. AIDS 2026. Poster abstract WEPEA004.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=9175
8. Mahomed S et al. Safety and preliminary efficacy of 6-monthly subcutaneous CAP256V2LS plus VRC07-523LS for HIV prevention in African women: results of the CAPRISA 012C phase 2 randomised controlled trial. AIDS 2026. Oral late-breaking abstract OAX1104LB.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=12779