A pioneering gene therapy study using adeno-associated virus (AAV) vectors demonstrated that a single injection of broadly neutralizing antibody (bNAb) genes delivered at birth can provide sustained protection against HIV-1 in infant rhesus macaques. Treated animals expressed protective antibodies for up to four years and were shielded from simulated breastfeeding and sexual transmission. Exploiting early life immune tolerance allowed for durable gene expression without immune rejection. This approach offers a promising one-time intervention to prevent pediatric HIV infection, particularly in resource-limited settings where maternal ART adherence is challenging.