A clinical trial led by The Rockefeller University and collaborators has demonstrated that HIV can be suppressed for more than three years in some patients using broadly neutralizing antibodies (bNAbs), according to findings published in a recent study. The research, conducted under the RIO trial framework, revealed that a single or double dose of bNAbs enabled participants to maintain undetectable viral levels without daily antiretroviral therapy (ART) for extended periods, with one individual remaining off treatment for 160 weeks (over three years). The results, detailed in a paper in Nature, suggest a potential shift in HIV treatment strategies by leveraging the immune system’s response.
Rockefeller-Led Study Shows HIV Suppression for Over Three Years via Antibody Therapy
Key Trial Details and Participant Outcomes
The RIO trial, a phase 2, randomized, placebo-controlled, double-blinded study, enrolled 68 men living with HIV who had been on suppressive ART for at least one year. Participants received either two long-acting bNAbs or a placebo before a monitored ART interruption. Initial findings indicated that most participants maintained undetectable viral loads for up to 20 weeks without ART, with some experiencing longer suppression. One participant, whose bNAbs had cleared from their system, remained off ART for 160 weeks, according to Marcilio Fumagalli, a postdoctoral associate at Rockefeller’s Nussenzweig lab. They’ve been washed out,
Fumagalli said, yet he still does not need ART.
The study also highlighted the role of the immune system in sustaining viral control. Researchers found that bNAbs appeared to “train” the immune system to act as a secondary defense, with natural immune activity working in tandem with the antibodies to suppress the virus. This synergy may explain the prolonged suppression observed in some cases.
Understanding the Viral Reservoir and Immune Response
One of the trial’s critical insights involved the latent HIV reservoir, a pool of dormant virus that traditional ART cannot eliminate. The study revealed that bNAb therapy significantly accelerated the decline of intact proviruses, reducing their half-life from 4–7 years during ART to 36 weeks. This suggests a potential pathway to eradicating the reservoir, a major barrier to an HIV cure. Michel C. Nussenzweig, head of Rockefeller’s Laboratory of Molecular Immunology, noted that participants with pre-existing neutralizing antibodies against HIV showed enhanced viral control, indicating that innate immune responses could amplify the effects of bNAbs.
The trial’s rigorous design included ethical oversight by multiple regulatory bodies, including the London–Westminster Research Ethics Committee and the UK Medicines and Healthcare products Regulatory Agency. Participants were selected based on strict criteria, such as initiating ART during primary HIV infection and maintaining suppressive treatment for at least one year prior to enrollment.
Implications for Future HIV Therapies
The findings offer hope for a new approach to HIV management, potentially reducing reliance on lifelong daily medication. By combining bNAbs with the body’s natural defenses, the study underscores a strategy that could minimize the viral reservoir and extend periods of viral suppression. However, the researchers emphasize that further studies are needed to validate these results in larger, more diverse populations. The RIO trial’s data, published in Nature, provides a foundation for developing therapies that harness both antibody and immune system mechanisms to combat HIV.