Overview: A new immunotherapy approach in HIV
Researchers report promising safety data from the first-in-human trial of an anti-PD-1 antibody, budigalimab, in people living with HIV. The study, published in Nature Medicine, explored whether a cancer immunotherapy could be used at low doses to augment the immune system’s ability to control HIV without daily antiretroviral therapy (ART). The results suggest that for a subset of participants, this strategy may delay viral rebound after stopping ART, offering a potential path toward drug-free control of the virus in the future.
What the trial tested
The randomized, placebo-controlled, double-blind Phase 1b study enrolled 41 participants across 11 sites in the United States, Canada, and Australia. The aim was to assess safety and tolerability of budigalimab, a monoclonal antibody that targets the PD-1 pathway—a braking mechanism that can exhaust T cells in chronic HIV infection. Using low doses, the trial sought to balance immune activation with safety, a critical concern for people living with HIV who also take ART.
Key findings and what they mean
Adverse events were generally mild to moderate, allowing the study to advance to a Phase 2-like stage. Importantly, six of the 11 participants who received budigalimab in the second stage experienced a delayed return of the virus after ART interruption, and two remained off ART for more than six months without rebound. No such benefit was seen in the placebo group. While this does not indicate a cure, it points to a potential for partial immune reconstitution that can help the body keep the virus at bay without daily medication in some individuals.
Why PD-1 blockade matters in HIV
The PD-1 pathway acts as a brake on T cells, and its chronic engagement in HIV can lead to T cell exhaustion. Blocking PD-1 aims to “re-energize” these immune cells, helping them recognize and control HIV more effectively. This approach has long been studied in cancer, where PD-1 inhibitors have boosted anti-tumor immune responses. In HIV, the hope is that a safer, low-dose immunotherapy could complement ART or even permit short-term interruptions without compromising control of the virus.
What the results mean for future research
As Dr. Jean-Pierre Routy notes, the findings indicate that the immune system can be trained to maintain control even after the anti-PD-1 drug becomes undetectable. The authors emphasize that this is a partial effect observed in a specific subset of participants. The next steps will involve larger, more diverse cohorts and combination strategies with other immunotherapies to identify who is most likely to respond and how to sustain benefit over time.
Limitations and next steps
Most trial participants were cisgender men, underscoring the need for more inclusive research, including women and people with different hormonal backgrounds. Further studies are needed to determine the durability of viral control, optimal dosing regimens, and how these therapies might be integrated with existing ART or used in structured periods of drug absence. The current results are encouraging but not definitive, and ongoing trials will test whether this approach can be refined into a reliable, scalable strategy for functional HIV cure.
A Montreal connection and the road ahead
The PD-1 pathway was first identified by a Nobel Prize–winning scientist, with Montreal researchers among the early pioneers showing in HIV patient cells that PD-1 blockade could restore immune responses. This early work laid the groundwork for the present clinical exploration of budigalimab’s potential in HIV management.
Conclusion: A hopeful step, with more questions to answer
While the results do not indicate a cure, they provide a meaningful proof of concept: boosting the immune system through targeted PD-1 inhibition may enable periods of drug-free viral control for some people living with HIV. If future trials validate these findings and identify the right patient populations, this approach could complement ART and improve long-term quality of life for many individuals.
