HIV infection remains a serious global problem. Although anti-retroviral therapy (ART) has made great strides toward controlling infection for many patients, HIV typically persists indefinitely requiring infected individuals to remain on expensive drug regimens for life and face life-long societal stigmas. The ability of ART to reconstitute normal immune system function remains highly variable, with many patients becoming resistant to standard-of-care drugs over time. Such individuals are at risk of cardiovascular disease, cancer and higher HIV reservoirs that can pass infection to non-infected individuals.
We have identified a unique subset of long-lived CD4+ T cells (RORA T-cells) that maintain stem-ness and self-renewal. The potential of these cells as a new HIV therapy is supported by clinical studies in which CCR5-gene edited CD4 T cells infused into patients resulted in a decline (up to 3 logs) of cells with integrated HIV DNA. Also observed was an associated rise in stem-like CCR5-ablated cells . A follow-up randomized clinical trial (TRAILBLAZER, NCT03666871) is ongoing with a cohort and a control arm to further evaluate the possible impact of CCR5-gene edited RORA T-cells on T cell homeostasis and HIV reservoir decay in the absence of ART .
We believe CCR5-edited RORA T-cells have potential to be a new class of HIV therapeutic that may provide sustained ART-free HIV remission and restoration of immune T cell homeostasis. Should future clinical trials be successful, this approach may provide a path toward a “functional cure” from HIV infection for many patients.