Half the participants from placebo arm of HIV cure trial have prolonged viral load remission when given broadly neutralising antibodies

In the second phase of the RIO HIV cure trial, participants originally given a placebo were offered the experimental therapy, the Conference on Retroviruses and Opportunistic Infections (CROI 2026) heard last week. More than half of them responded with a prolonged period of low or undetectable viral load and were able to put off resuming their HIV therapy for more than 20 weeks. Two are still off antiretroviral therapy (ART) after more than a year.

At last year’s CROI, one of the most important presentations concerned the first phase of RIO. It randomised 68 people on stable ART to receive either two broadly neutralising antibodies (bnAbs) or a placebo. They then stopped their ART, in an analytical treatment interruption (ATI). Twenty-two of the 34 recipients (65%) had not reached the viral load criteria for restarting ART by week 20 of the ATI, compared to just two of those receiving placebo, and a high proportion were still off ART a year later. One participant has now been undetectable off ART for four years. This trial has now been published as a preprint, and was chosen as one of the 11 most significant clinical trials of last year by Nature Medicine.

But what about the people who received a placebo? In RIO’s second phase, presented to CROI 2026 by Julia Edgar of the University of Oxford, the 34 people who had received a placebo in phase one were given the chance to receive the two antibodies, teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). They received two infusions of both bnAbs 20 weeks apart while on ART and then stopped their ART 24 weeks after the second bnAb dose.

This was slightly different to the first phase of the trial (RIO A), in which the participants stopped their ART just after receiving the bnAbs (or placebo). The reason for delaying the ATI for another 24 weeks in the second phase (RIO B), which was not placebo controlled, was to ensure that no significant levels of the bnAbs were left in the body before the ATI started. This meant that if participants’ HIV viral load took a long time to ‘rebound’ to normal levels, the researchers would know that it was not due to the bnAbs acting like antiretrovirals and directly suppressing the virus, but because they had induced immunological changes that might be used to guide further cure studies. In the video accompanying this article, Professor John Frater explains this ‘vaccinal effect’.

All 28 participants had virally rebounded within 20 weeks when they took a placebo in the initial trial. In RIO B, 13 of the 28 (46%) rebounded rapidly and restarted their ART within nine weeks (typically, 95% of people who stop ART rebound within six weeks).

But none of the 15 others (54%) had rebounded 20 weeks after stopping their ART. Six had not rebounded by week 39, and five maintained viral loads below or around 1000 for a year. Three of the five restarted ART but two are still on their ATI, including one who has maintained a completely undetectable viral load (below 50) for the whole year (so may be on the way to joining the long-term controller from RIO A).

The peak viral load of the placebo recipients in RIO A was around 100,000. In RIO B, it was scarcely lower in the fast rebounders (about 80,000), but even after rebound was more than 10 times lower in the slow rebounders (about 7000).

If the figure of 54% non-rebounders after 20 weeks off ART in RIO B looks less impressive than the 65% in RIO A, it should be remembered that in RIO A, participants had just received bnAbs (or placebo) when they stopped their ART, so for some of the time their bnAbs would be directly suppressing the virus. In RIO B, ART was stopped almost six months after taking bnAbs, so they couldn’t have this effect, but may have induced immunological changes.

Further studies will look at these immunological changes in RIO B participants, to find out in detail how viral rebound was delayed in just over half of them.

Julia Edgar also announced a third part of the RIO trial. In this trial, people on ART will have two ATIs with a period on ART in between; then they will take the two bnAbs and have another period on ART before a third ATI. The object of this trial is to test a hypothesis that periods of viraemia may re-sensitise the immune system to HIV and generate a population of fresh T-cells that will additionally contribute to further delaying viral rebound – a possibility outlined in two recent articles reported by aidsmap.

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