April 30, 2026 —
A novel approach using Adeno-associated virus (AAV) to deliver long-acting antibodies may offer a new path toward functional control of HIV, according to a preclinical study from Oregon Health & Science University. Published in Science Translational Medicine, the research demonstrates that AAV-mediated expression of a CCR5-blocking antibody can sustain antiviral activity and suppress virus replication over extended periods in SHIV-infected macaques.
While combination antiretroviral therapy (cART) has transformed HIV into a manageable chronic condition, it requires strict lifelong adherence and does not eliminate viral reservoirs. Even short interruptions in treatment can lead to viral rebound. To address these limitations, researchers engineered an AAV-based system to deliver leronlimab, an antibody that targets the CCR5 receptor—a key entry point used by HIV to infect CD4+ T cells. By enabling continuous in vivo production of the antibody, this strategy aims to replace repeated dosing with a durable, long-term therapeutic effect.
In the study, 19 SHIV-infected rhesus macaques received AAV vectors encoding leronlimab. Nearly all animals achieved detectable antibody expression following treatment. In those that did not mount a significant immune response, antibody levels remained stable for more than a year. However, a subset of animals developed anti-drug antibodies (ADA), which reduced or eliminated therapeutic expression, highlighting a key challenge for this approach.
Among macaques that achieved sufficient antibody levels, the results were particularly encouraging. Six out of nine animals demonstrated long-term partial or complete suppression of viral replication. In the remaining animals, additional dosing of leronlimab led to either full viral suppression or a significant reduction in viral load. These findings suggest that reaching a critical threshold of antibody expression is essential for effective CCR5 blockade and sustained viral control.
Despite these promising results, several challenges remain. Immune responses against the expressed antibody may limit durability in some patients, and further optimization of AAV capsids, promoters, and dosing strategies will be required to achieve consistent therapeutic levels. Researchers also note that combining AAV-delivered antibodies with other antiviral approaches could further enhance efficacy and durability.
Overall, this study highlights the potential of AAV-based gene therapy to move beyond chronic disease management toward a functional cure strategy for HIV. By enabling long-term, endogenous production of antiviral antibodies, this approach could reduce or eliminate the need for daily treatment. While still in the preclinical stage, the findings underscore the expanding role of gene therapy in addressing complex, chronic infectious diseases.
