Adeno-associated virus gene therapy-mediated CCR5 blockade suppresses virus replication long term in SHIV-infected macaques.

T cells, AAV-leronlimab drove stringent or partial control of SHIV viremia in six macaques long term. In the three macaques with uncontrolled SHIV viremia, short-term administration of exogenous leronlimab induced complete SHIV suppression in two and a 100-fold reduction in the third, indicating that a threshold of leronlimab expression is necessary to effectively halt SHIV replication. These results demonstrate the potential of gene therapy-mediated long-term antibody-based CCR5 blockade for HIV functional cure but highlight challenges in achieving sufficient antibody expression when targeting an abundant self-antigen.