Results from a phase 2 clinical trial show that broadly neutralizing antibodies can suppress HIV long-term, keeping virus levels undetectable for months and even years. The therapy appears to prompt patients’ immune systems to control the infection and accelerates the decline of the latent viral reservoir.
Antiretroviral therapy transformed HIV from a fatal diagnosis into a manageable chronic condition, but it remains unable to eliminate dormant viral cells that persist for decades. Now, new data from a prominent clinical trial offers an alternative path forward. Researchers found that administering one or two doses of targeted antibodies can suppress the virus over extended periods without daily medication.
The RIO Trial Design and Participant Outcomes
The trial, known as the RIO study, randomized 68 men living with HIV to receive either two long-acting broadly neutralizing antibodies—specifically 10-1074-LS and 3BNC117-LS—or a placebo. Before receiving the infusion, participants underwent a closely monitored pause in the daily antiretroviral therapy they had taken since their initial infections. The research was led by The Rockefeller University, Imperial College London, and the University of Oxford. As detailed in Nature Medicine, the trial was funded by the Gates Foundation and Rockefeller’s Stavros Niarchos Institute of Infectious Diseases, and was a randomized, placebo-controlled, double-blinded phase 2 study that enrolled individuals aged 18 to 60 years across multiple HIV clinical research sites in the United Kingdom and one site in Denmark.
Initial data showed that a single dose allowed most participants to maintain undetectable viral levels for up to 20 weeks without daily treatment. Individuals maintaining suppression were given the option to receive a second dose at that milestone. Half of those participants remained undetectable at 48 weeks, and one-third maintained suppression at 72 weeks.
Beyond complete viral suppression, researchers documented another distinct pattern among 29 participants who eventually developed detectable virus after receiving the antibodies. According to trial data, 38 percent of those individuals exhibited fluctuating viremia,
a pattern where HIV repeatedly rose and fell at low levels without meeting the criteria required to restart standard daily medication. This phenomenon persisted for as long as 58 weeks.
Immune System Response and Viral Reservoir Reduction
The implications of the trial extend beyond temporary suppression, suggesting the antibodies might alter how the body interacts with the virus over time. Investigators observed that participants who already possessed their own neutralizing antibodies against HIV were better equipped to control the infection, pointing to a cooperative effect between natural immunity and the administered treatment.
Laboratory analysis of blood samples collected throughout the study also revealed changes within the latent viral reservoir—the pool of dormant cells capable of reigniting an infection. While the initial size of this reservoir did not predict how long participants remained off daily treatment, intact proviruses declined with an estimated half-life of just 36 weeks following the antibody therapy. By comparison, standard antiretroviral therapy yields a reservoir half-life of four to seven years, according to findings published in Nature Medicine.
Extended Control and Future Implications
The durability of the immune response continues to surprise researchers analyzing the trial cohorts. In some cases, the administered antibodies cleared the body entirely weeks or months prior, yet patients maintained viral control without resuming standard treatment regimens.
Researchers emphasize that these findings offer foundational insights into how future therapeutic strategies might harness a patient’s natural immune mechanisms to manage or eventually clear HIV infection.
