RIO Study Suggests Antibodies Could Offer a Break from Daily HIV Treatment

In a significant breakthrough for HIV cure research, a new study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 suggests that long-acting antibodies could allow some people with HIV to stay off daily antiretroviral therapy (ART) for extended periods. The RIO study, a randomized, placebo-controlled clinical trial, found that a combination of two broadly neutralizing antibodies (bNAbs) effectively delayed viral rebound after stopping ART, providing important insights into strategies for functional HIV remission.

A Potential Alternative to Daily HIV Medications

For decades, daily ART has been the gold standard for managing HIV, preventing the virus from replicating and allowing people with HIV to live long and healthy lives. ART requires strict adherence, as missing doses can lead to viral rebound and drug resistance. Scientists have long searched for alternative strategies that could offer people with HIV greater flexibility in managing their treatment.

The RIO study tested whether two bNAbs — 3BNC117-LS and 10-1074-LS — could help maintain viral suppression in people with early-treated HIV, after stopping ART. While some studies are evaluating bNAbs in combination with long-acting antivirals for HIV treatment, RIO focused on their potential role in post-treatment viral control as part of an HIV cure strategy.

The trial enrolled 68 participants, all of whom had begun ART soon after their diagnosis and had well-controlled viral loads. Participants were randomly assigned to receive either:

• Two doses of the bNAb combination, administered intravenously over several months, or
• A placebo, with no active treatment.

After receiving their assigned treatment, all participants stopped taking ART to evaluate whether the antibodies could keep the virus in check.

Findings: A Longer Period Off ART for Many

The study results were striking. By 20 weeks after stopping ART,

• 75% of those who received the antibodies had not experienced viral rebound, compared to just 9% in the placebo group.
• Some participants remained off ART for over a year, with 21% still controlling the virus at 72 weeks.
• Six participants in the bNAb group showed no viral rebound even after their last dose of antibodies.

Dr. Sarah Fidler, who led the study, emphasized the potential impact of these findings:

“What we see is a strong delay in viral rebound among those receiving bNAbs. The data suggests that in some cases, the antibodies may help the immune system control the virus more effectively, extending the time people can remain off ART.”

Although not a cure itself, this study supports ongoing efforts to develop strategies for functional HIV remission—where the virus remains controlled without the need for daily ART.

Could This Be Used Worldwide?

One of the biggest questions surrounding this approach is whether it could be used globally, including in lower-income settings, such as sub-Saharan Africa, where the burden of HIV remains high.

Dr. Fidler acknowledged that while bNAb-based immunotherapy is not yet ready for widespread use, there is reason to be optimistic.

“If we find the right combination of antibodies, matching a person’s specific strain of HIV, this could be much more feasible to roll out. A large study in South Africa tested similar antibodies for HIV prevention and showed they can be delivered in different settings. We’re not quite there yet, but the potential is very exciting.”

If successful, this approach could reduce reliance on daily ART, making HIV treatment and remission strategies more accessible to people who face challenges with lifelong medication adherence.

Safety and Future Considerations

The study also found that the treatment was safe and well-tolerated:

• Nine serious adverse events were reported, including one death, but none were linked to the study treatment.
• 94% of those who restarted ART regained full viral suppression within 12 weeks.
• No immune rejection of the antibodies was detected.

Experts at the conference raised important questions about the long-term feasibility of bNAbs. Dr. Laura Waters, a leading HIV researcher with the NHS in London, asked whether people with underlying health conditions should have been included in the study.

Dr. Fidler acknowledged the concern:

“We excluded individuals with major comorbidities, but future studies will need to look at how bNAbs interact with other health conditions. Biomarkers like IL-6 and CRP, which indicate inflammation, may help guide treatment decisions.”

Another critical question concerned how the virus rebounded in participants. A researcher asked whether the pattern of rebound differed between the placebo group and those who received bNAbs.

Dr. Fidler explained that the placebo group rebounded quickly and at high levels, leading most participants to restart ART immediately.

“In contrast, those receiving bNAbs had a much slower and more controlled rebound, with some staying undetectable for much longer,” she noted.

A Step Toward Long-Term HIV Remission?

The study’s findings raise broader questions about the potential role of bNAbs in HIV cure research. Could this approach eventually replace daily ART for some individuals?

One of the key questions raised at CROI was whether bNAbs are preventing viral rebound primarily through direct action against HIV, or whether they are also boosting the body’s own immune response.

Dr. Fidler acknowledged that it’s likely to be a combination of both factors:

“We are still analyzing the immune data, but we see hints that bNAbs may be enhancing HIV-specific T-cell responses, which could help explain why some people remain off ART longer.”

However, there are still hurdles to overcome. Resistance to bNAbs remains a challenge, and researchers are still working to determine how many people could benefit from this approach.

What’s Next?

While the the RIO study provides important insights into HIV cure strategies, additional research is needed to determine:

• How long bNAbs can keep the virus suppressed
• Whether this approach could work for a broader group of people, including those with underlying health conditions
• How to prevent resistance to bNAbs over time

Future studies may explore whether combining different bNAbs or adding immune-boosting therapies could extend viral suppression even further.

For now, the results of the RIO study represent a promising step forward in HIV cure research, offering valuable data on how bNAbs might be used to help people control HIV without daily medication. While ART remains the most effective strategy for managing HIV, these findings suggest that for some, long-acting antibodies could contribute to functional cure strategies—bringing us closer to a future with more treatment and remission options.