HIV-specific and resistant CAR T cells promote control of HIV replication in people with HIV

We conducted a first-in-human evaluation of HIV-specific, HIV-resistant chimeric antigen receptor (CAR) T cells (CARTs) to determine their capacity to modulate viral rebound dynamics following analytic treatment interruption (ATI). Among ten treated individuals who received engineered T cells, one individual did not rebound during the ATI and had a remarkable expansion of their CARTs 43 days after the start of the ATI, suggesting that the CARTs recognized rebounding HIV and prevented its spread. Post-rebound virologic control was observed in 1 participant for 90 weeks and another 5 participants had remarkable reductions in their viral load after viral peak was reached, maintaining viral loads below their set point. CART infusion was associated with broad reinvigoration of endogenous HIV-specific CD8 T cell responses, and immune escape to one of these responses was documented. Together, these findings show that HIV-specific CARTs can be an integral component in HIV Cure strategies.