NK cell immunotherapy administered at the time of HIV recrudescence is associated with viral control

One barrier to developing an HIV-1 cure is viral reservoirs persisting within B cell follicles of lymphatic tissues, partly due to failure of HIV-specific cytotoxic cells to express the follicular-homing receptor CXCR5. We evaluated HIV-specific CAR/CXCR5 NK cells armored with IL-15 and a PD-1 knockout for in vitro functionality. The safety and efficacy of these NK cells were assessed in vivo by treating ART-suppressed, HIV-infected-humanized-DRAGA mice following ART interruption. In vitro, CAR and control NK cells proliferated and killed HIV-Envelope-expressing cells. In vivo , there were no adverse health outcomes associated with cell infusions. CAR NK-treated animals had, on average, 1.88 times higher NK cell levels, and cells persisted up to 2 weeks longer than control NK-treated animals. At 56 days post-treatment, 62.5% of CAR NK-treated and 50% of control NK-treated groups had viral loads below the detection limit compared to 0% of the saline control group. Importantly, animals that had undetectable viral loads at 56 days post-treatment had earlier viral rebound post-ART interruption that coincided with high levels of NK cells, suggesting that timing of treatment with viral recrudescence was key to efficacy. This study demonstrates the promise of NK therapies for treating HIV infections.