Single AAV Gene Therapy Injection at Birth Shows Potential for Long-Term HIV Protection in Newborns

NEW ORLEANS, LA – July 30, 2025 – A groundbreaking study published in Nature offers new hope in the fight against pediatric HIV, demonstrating that a single adeno-associated virus (AAV) gene therapy injection delivered at birth could provide years of protection. This approach leverages the unique immunological window of tolerance in early life, potentially revolutionizing prevention strategies in high-risk regions.

The research, led by first author Amir Ardeshir, Associate Professor of Microbiology and Immunology at the Tulane National Primate Research Center, alongside colleagues from the California National Primate Research Center, explored a novel method to protect newborns from HIV infection. “Nearly 300 children are infected with HIV each day,” stated Professor Ardeshir. “This approach could help protect newborns in high-risk areas during the most vulnerable period of their lives.”

The study, conducted in nonhuman primates, utilized an AAV to deliver genetic code to muscle cells. These cells were reprogrammed to continuously produce broadly neutralizing antibodies (bNAbs) capable of fighting multiple HIV strains. This innovative method addresses a long-standing challenge with bNAbs, which previously required costly and logistically complex repeated infusions. As Professor Ardeshir explained, “Instead, we turn these muscle cells – which are long-lived – into micro factories that just keep producing these antibodies.”

Crucially, the timing of the treatment proved vital for long-term protection. Subjects who received the AAV gene therapy within their first month of life were protected from infection for at least three years without needing a booster, suggesting potential coverage into adolescence in humans. In contrast, those treated at 8-12 weeks, with more developed immune systems, showed less effective acceptance of the treatment.

“This is a one-and-done treatment that fits the critical time when these mothers with HIV in resource-limited areas are most likely to see a doctor,” Professor Ardeshir emphasized. “As long as the treatment is delivered close to birth, the baby’s immune system will accept it and believe it’s part of itself.”

More than 100,000 children acquire HIV annually, predominantly through mother-to-child transmission post-birth via breastfeeding. While antiretroviral treatments exist, adherence and access to care decline after childbirth in resource-limited settings.

The study also observed that exposing fetuses to antibodies before birth could aid older infants in accepting the gene therapy later, mitigating immune rejection. However, the researchers believe a single injection at birth offers the most cost-effective and feasible real-world solution, minimizing the burden on mothers for follow-up visits.

While questions remain regarding the direct translation of these results to human infants—who may respond differently to AAV-delivered treatments—and the study’s focus on a single simian-human immunodeficiency virus strain, the implications are profound. If successful, this AAV gene therapy could dramatically reduce mother-to-child HIV transmission rates, particularly in regions like sub-Saharan Africa, where 90% of pediatric HIV cases occur. This platform also holds potential for adaptation to protect against other infectious diseases such as malaria.

“Nothing like this was possible to achieve even 10 years ago,” Professor Ardeshir concluded. “This was a huge result, and now we have all the ingredients to take on HIV.”