Gene therapy shows promise for HIV control without drugs

U.S. researchers said Wednesday they have used gene therapy involving genetically engineered T- cells to successfully decrease the amount of the AIDS virus in several patients taken off antiretroviral drug therapy (ADT) entirely, including one patient whose levels became undetectable. The study, published in the U.S. journal New England Journal of Medicine, is the first published report of any gene editing approach in humans, the researchers said. "This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs," senior author Carl June, professor of the University of Pennsylvania, said in a statement. "This reinforces our belief that modified T cells are the key that could eliminate the need for lifelong ADT and potentially lead to functionally curative approaches for HIV/AIDS," June said. In their study, the researchers used a technology called the zinc finger nuclease (ZFN) to modify the T cells in 12 patients with the AIDS virus in order to mimic the CCR5-delta-32 mutation that can provide a natural HIV resistance. Only one percent of the general population carries that rare mutation. They then infused the modified cells known as SB-728-T into two groups of patients, all treated with single infusions of about 10 billion cells, between May 2009 and July 2012. Six were taken off antiretroviral therapy altogether for up to 12 weeks, beginning four weeks after infusion, while six patients remained on treatment. The researchers found that the amount of HIV dropped in four patients whose treatment was interrupted for 12 weeks. One of those patients' viral loads dropped below the limit of detection before reinstitution of ADT and the patient was later found to be "heterozygous" for the CCR5-delta-32 gene mutation, they said. "This case gives us a better understanding of the mutation and the body's response to the therapy, opening up another door for study," co-author Bruce Levine, associate professor of the University of Pennsylvania said. Therapies based on the CCR5 mutation have gained steam over the last six years, particularly after a man known as the Berlin Patient was "functionally" cured. Diagnosed with acute myeloid leukemia, the man received a stem cell transplant from a donor who had the CCR5 mutation and has remained off ADT since 2008.