CROI 2026: Second course of bNAbs slows viral rebound and to lower peak levels in RIO study

CROI 2026 included new results from the second stage of the RIO study using immune-based treatments in people who were diagnosed and treated in early HIV infection. [1]

The two broadly neutralising antibodies (bNAbs) in RIO are 3BNC117 and 10-1074, and their impact on maintaining suppressed viral load was monitored after stopping HIV meds during one or more analytical treatment interruptions (ATI).

Last year at CROI, the results from Stage 1 of the randomised (1:1), double-blind placebo-controlled study were presented from 68 participants. [2]

This year, results were presented from 28 participants in Stage 2, including 7 in the placebo arm who had the chance to receive bNAbs after Stage 1 and 21 participants in the original active arm who had the choice to receive bNAbs a second time. This allowed for comparisons in viral load dynamics both (i) between groups and (ii) using paired comparisons within groups.

Median bNAb levels in the 7 Arm A participants were similar at the beginning of Stage 2 at <50 ug/mL to when viral load rebounded in Stage 1 (i.e. below the threshold level for effect).

Results overall showed that participants were much less likely to rebound in ATI 2 compared to ATI 1 (50% vs 100%) with HR 0.17 (95%CI 0.08 to 0.35) p<0.0001, and with many maintaining low-level viraemia rather than rapidly rebounding.

The median viral load peak was also significantly lower (p=0.0003) and the viral load doubling time was significantly slower (p=0.006) after ATI 2 compared to after ATI 1, although some participants had other responses.

ATI 2 generated either early viral load responses within 9 weeks or slower drawn out responses over 48 weeks and longer. Although there were no differences between early viral load responses after ATI 2 compared to ATI 1, there were significant differences in participants with slower viral load rebound with lower viral load peaks (p<0.001) and slower doubling time (p=0.011).

The ongoing Arm C of the RIO study is looking further at the dynamics of viral rebound and responses in relation to timing of ATI and bNAbs in a new cohort of 18 participants.

Both bNAbs in RIO were produced at Rockefeller University and are now in development at Gilead.