New Immunotherapy Approach Sparks Hope for HIV Management
Researchers have taken a bold step in the hunt for HIV strategies that could reduce or even eliminate the need for daily antiretroviral therapy (ART). A first-in-human, randomized, placebo-controlled Phase 1b trial published in Nature Medicine explored budigalimab, a monoclonal antibody that targets the PD-1 protein, a key immune checkpoint. The study, conducted across 11 sites in the United States, Canada, and Australia, sought to determine whether a cancer-style immunotherapy could safely boost the immune response against HIV and possibly enable short-term, drug-free viral control after ART interruption.
What the Study Found
Participants with well-controlled HIV on suppressive ART received low-dose budigalimab over two stages. The doses were intentionally lower than those used in cancer therapy to prioritize safety and tolerability for people living with HIV. The primary outcome—safety and tolerability—was favorable, allowing progression to a second stage and opening the door to look for signals of viral control after ART interruption.
In the second stage, six of eleven participants who received budigalimab showed a delayed return of the virus after stopping ART, and two remained off ART with no viral rebound for more than six months. Importantly, no such viral control was observed in the placebo group. Dr. Jean-Pierre Routy and colleagues emphasized that these results do not constitute a cure; rather, they indicate that a portion of participants could sustain partial or intermittent control of HIV after treatment-induced immune activation wanes.
How PD-1 Inhibition Could Help
PD-1 is a protein that serves as a brake on T cells, which are crucial to attacking HIV-infected cells. In people living with HIV, PD-1–mediated exhaustion diminishes immune capacity to clear the virus. Blockading this pathway with a PD-1 inhibitor like budigalimab can potentially reinvigorate T cells, enabling a more effective and durable immune response against HIV. The study’s authors note that some participants maintained control even after the drug was no longer detectable, suggesting the immune system may be reconditioned to keep HIV in check without continuous drug exposure.
Clinical and Practical Implications
While the findings are encouraging, they are early and limited to a subset of participants. The trial’s stage 2 data point toward the possibility of combining PD-1 blockade with other immunotherapies or immune-modulating strategies to broaden responder rates. Long-term safety, optimal dosing, and the identification of predictive biomarkers will be critical in guiding future trials and potential clinical use.
Another key takeaway is the potential impact on treatment timelines. If immunotherapy can enable periods of drug-free viral control, some people might experience reduced ART burden, improved quality of life, and possibly fewer stigma-related barriers to adherence. However, the current results should be interpreted cautiously until larger, more diverse cohorts confirm the effect and clarify who is most likely to benefit.
Diversity and Future Research
The study cohort was predominantly cisgender men, highlighting the need for more inclusive research that reflects the full demographic spectrum affected by HIV. Future trials should actively recruit women and other underrepresented groups to determine whether hormonal and genetic factors influence response to PD-1 blockade in HIV.
Historical Context and Development Path
PD-1’s discovery earned a Nobel Prize for Tasuku Honjo in 2018, and Montreal researchers helped lay the groundwork by showing that blocking PD-1 could restore HIV-specific immune responses in laboratory models. The current trial builds on those insights, translating a cancer immunotherapy approach into the HIV field with careful attention to safety and tolerability in a non-cancer population.
Researchers acknowledge that achieving a durable, drug-free control of HIV for all patients remains a distant goal. Yet the study’s success in identifying a subset of responders, along with clear safety signals for low-dose regimens, marks a meaningful advance in the quest for a functional HIV cure.
Overall, budigalimab’s Phase 1b results illuminate a promising path forward. If subsequent studies confirm these signals and refine patient selection, immunotherapy could become a valuable component of multi-pronged strategies toward long-term HIV control beyond daily ART.
About the Study
“Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study” was published in Nature Medicine. The trial was sponsored by AbbVie and led by an international team including researchers from McGill University Health Centre and Université de Montréal.
