HIV Cure Trial Shows 54% of Placebo Recipients Achieve Prolonged Viral Remission After Receiving Experimental Therapy
Key Insights
More than half of participants who initially received placebo in the RIO HIV (search) cure trial achieved prolonged viral load remission lasting over 20 weeks when given experimental broadly neutralizing antibodies in the second phase.
Two participants remain off antiretroviral therapy after more than a year, with one maintaining completely undetectable viral load throughout the entire year-long period.
The delayed viral rebound appears to result from immunological changes induced by the antibodies rather than direct viral suppression, providing insights for future HIV (search) cure research.
The second phase of the RIO HIV (search) cure trial has demonstrated that more than half of participants who initially received placebo achieved prolonged viral load remission when subsequently given experimental broadly neutralizing antibodies. The results, presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2026), show that 15 of 28 participants (54%) maintained viral suppression for more than 20 weeks after stopping antiretroviral therapy, with two individuals remaining off treatment for over a year.
Trial Design and Methodology
In the second phase of RIO (RIO B), the 34 participants who had received placebo in the initial trial were offered the experimental therapy consisting of two broadly neutralizing antibodies: teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). Participants received two infusions of both antibodies 20 weeks apart while continuing their antiretroviral therapy, then stopped ART 24 weeks after the second antibody dose.
This design differed from the first phase (RIO A), where participants stopped ART immediately after receiving the antibodies or placebo. The 24-week delay in RIO B was implemented to ensure no significant levels of the antibodies remained in the body before the analytical treatment interruption began, allowing researchers to distinguish between direct viral suppression and immunological changes.
Sustained Viral Control Results
Of the 28 participants in RIO B, 13 (46%) experienced rapid viral rebound and restarted ART within nine weeks. However, none of the remaining 15 participants (54%) had rebounded by week 20 after stopping ART. Six participants maintained viral suppression through week 39, and five sustained viral loads below or around 1,000 copies/mL for a full year.
Notably, two participants continue their treatment interruption after more than a year, including one who has maintained a completely undetectable viral load (below 50 copies/mL) throughout the entire year-long period. This individual may be joining the long-term controller from RIO A, who has now been undetectable off ART for four years.
Viral Load Dynamics and Immunological Impact
The viral load patterns revealed significant differences between participant groups. While all 28 participants had experienced viral rebound within 20 weeks when they received placebo in the initial trial, the antibody treatment appeared to create lasting changes. Peak viral loads in fast rebounders reached approximately 80,000 copies/mL, similar to the 100,000 copies/mL observed in placebo recipients during RIO A. However, slow rebounders maintained peak viral loads more than 10 times lower at around 7,000 copies/mL.
According to Professor John Frater, the delayed viral rebound likely results from a "vaccinal effect" - immunological changes induced by the antibodies rather than direct viral suppression. This mechanism provides valuable insights for future HIV (search) cure research, as it suggests the therapy may enhance the immune system's ability to control HIV replication.
Clinical Significance and Future Research
The RIO trial's first phase, which randomized 68 people on stable ART to receive either the two broadly neutralizing antibodies or placebo, demonstrated that 22 of 34 recipients (65%) had not reached viral load criteria for restarting ART by week 20, compared to just two placebo recipients. This trial was selected as one of the 11 most significant clinical trials of the year by Nature Medicine.
While the 54% non-rebound rate in RIO B appears lower than the 65% in RIO A, researchers emphasize that the delayed treatment interruption in RIO B provides more meaningful data about sustained immunological changes. Future studies will examine these immunological modifications in detail to understand how viral rebound was delayed in over half of the participants.
The findings do not represent a cure and do not support treatment interruption outside clinical trials. However, they provide early evidence that immune-based interventions might modulate post-treatment viral control, offering new directions for HIV (search) cure research.