Infusion of CCR5-edited T cells Allows Immune Reconstitution and HIV Reservoir Decay

Hematopoietic stem cell transplantation from a donor whose T cells did not express CCR5—a co-receptor for HIV—resulted in an apparent cure of an HIV-infected adult1. Herein, we have exploited this strategy by adoptive transfer of autologous CCR5 gene disrupted CD4+ T cells (SB-728-T) in 9 HIV+ participants. A single infusion of SB-728-T, a minimally invasive intervention, led to sustained increases in CD4+ T cell counts through 3.5 years (33-44 months) compared to baseline (median increase of +193 cells/µl, P = 0.02). The degree of long-term immune reconstitution was associated with expansion of a polyclonal stem cell-like CCR5-depleted CD4+ T cell population. SB-728-T therapy was also associated with expansion of polyfunctional HIV-specific CD8+ T cells (P = 0.03) and decline in size of the HIV reservoir (-0.23 to -3.6 log decrease). Collectively, these data suggest that generation and protection of CD4 memory cells will improve T cell homeostasis, enhance HIV-specific immunity, and accelerate the decline of the host HIV reservoir. We studied nine HIV-infected adults on long-term cART who had a CD4+ T cell count between 200 and 500 cells/µL. Transcriptional analysis of CD4+ T cell memory subsets was performed at month 33-44 (at plateau) to determine if CD4 CD45RAintROint cells represented a memory subset distinct from CD45RA+RO- CD95+, TCM, and TEM subsets.