For this Phase 1/pilot clinical trial in HIV funded by CIRM and Sangamo Therapeutics and sponsored by City of Hope, eight  persons living with HIV (PLH) underwent a transplantation using their own stem cells modified by disruption of the CCR5 gene.  The absence of the CRR5 gene has been shown to protect against HIV infection. The goal of the study was to determine if this approach was safe and feasible.  In addition, the study attempted to determine if study participants who stopped the antiretroviral therapy would be protected from recurrence of HIV in their blood and whether the CCR5-disrupted blood cells would be protected from this HIV “rebound.”  

This was the first systematic trial of gene-editing of blood stem cells and used the method of zinc finger nucleases (ZFN) to edit the CCR5 gene followed by infusion of these cells after busulfan treatment. The study team has finalized the preliminary Clinical Study Report (CSR) with clinical trial data from the first 4 years of follow-up.  These are the preliminary conclusions from the study:

Genome editing of CCR5 in blood stem cells from PLH is feasible using the methods of this study.  The process was safe. Patients were given a low or a high dose of busulfan, and engraftment of the gene modified cells was improved at the higher busulfan dose. There was long-term expression of the disrupted CCR5 gene in peripheral blood and bone marrow. There is a low percentage of cells with CCR5 disruption, but as noted, this low level was maintained for the duration of the study.   We were able to perform an analytical treatment interruption, aka, stopping antiretroviral medication, in 4 study participants until their HIV viral load returned. Expression of HIV during this period did not appear to select for CCR5 disrupted cells.

In conclusion, this novel method of CCR5 disruption was shown to be safe and feasible.  Future improvements in this method will require more efficient gene editing tools, if HIV cure will be possible.