Whether a stem cell transplant using an HIV-infected person’s own genetically modified immune cells can become a cure for the disease is the focus of a new $20 million, five-year research grant award announced by the National Institutes of Health to the Fred Hutchinson Cancer Research Center.

Hutchinson Center researchers will use the grant to lead a multifaceted team of scientists and institutions to study whether a person’s own stem cells can be engineered to deny HIV entry into the body’s blood cells. The researchers also will work to develop tools to eradicate existing reservoirs of infection in the body.

“Funding for research to find a cure for HIV-infected persons represents a paradigm shift,” said Keith Jerome, M.D., Ph.D., an expert in viral infections and co-principal investigator of the grant. “HIV has been an incurable, lifelong infection that at best sentences people to a lifetime of complex drug therapies. Now the research field is shifting to address the possibility of a cure. No one would have talked about this approach five years ago.”

The Hutchinson Center grant was one of three announced by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to fund research focused on developing strategies for eradicating HIV infection via its Martin Delaney Collaboratory program.

The research projects will focus on ways around a major obstacle to long-term control and cure of HIV: the persistence of HIV provirus in reservoirs throughout the bodies of infected persons. The infected cells in these reservoirs are long lived and remain a threat during the lifespan of infected persons. Highly active antiretroviral therapy (HAART), although successful at keeping the spread of HIV under control by inhibiting viral replication, does not eliminate these reservoirs. If a patient discontinues HAART, the virus rebounds.

One approach under investigation is autologous stem cell transplantation, in which the infected patient’s own immune cells are genetically modified to be resistant to HIV by eliminating one of the receptors, called CCR5, which HIV needs to infect new cells.

A second approach involves developing DNA-targeting proteins to directly attack the reservoirs of HIV provirus without harming the infected cells themselves. This method would complement the stem cell-based approach and could potentially lead to elimination of the HIV provirus.

Another goal will be to optimize the combination of stem cell protection and HIV reservoir-purging techniques. Researchers expect to have enough data to begin human clinical trials in five years.