NK cell immunotherapy after analytic treatment interruption is associated with HIV viral control

Over 39.9 million individuals are living with HIV worldwide. There is a need to develop novel therapeutics to improve treatment or cure HIV. In this study, we evaluated HIV reservoir-targeting chimeric antigen receptor (CAR)/CXCR5 natural killer (NK) cells armored with IL-15 and PD-1 knockout as well as control activated NK cells for their safety and efficacy by treating antiretroviral therapy (ART)-suppressed, HIV-infected humanized DRAGA mice following ART interruption. There were no adverse health outcomes associated with cell infusions. At 56 days post-treatment (DPT), 62.5% of CAR NK-treated and 50% of control NK-treated groups had viral loads below the detection limit compared with 0% of the saline control group. CAR NK-treated animals had, on average, 1.88 times higher peak NK cell levels than control NK-treated animals, and elevated levels of NK cells persisted up to 28 DPT in treated animals. Importantly, animals that had undetectable viral loads at 56 DPT had earlier viral rebound post-ART interruption that coincided with high levels of NK cells, suggesting that timing of treatment with viral recrudescence may play a role in efficacy. This is the first study evaluating NK cell therapies in hDRAGA mice and demonstrates the promise of NK cell therapies for curing HIV.