amfAR, The Foundation for AIDS Research

Gene Therapy and the Potential for an HIV Cure

By Rowena Johnston, Ph.D.


September 10, 2010— Three years ago, an HIV patient in Berlin requiring treatment for leukemia received a stem cell transplant and the results changed the AIDS research world. Preparing for the procedure, his doctors searched for a donor who was not only a tissue match but also had a rare genetic mutation called CCR5 delta-32, which blocks HIV infection in almost all cases. Since the transplant, the patient has stopped taking antiretroviral therapy and no HIV has been detected in his body. He appears to have been the only person ever cured of HIV.

Active attempts to replicate this procedure in other AIDS patients with leukemia have been unsuccessful, for several reasons. First, the likelihood of finding a donor who is a tissue match and also has the delta-32 mutation has recently been estimated to be approximately one in 10 million. In addition, the chemotherapy and irradiation needed to prepare a patient to accept stem cells from an unrelated donor are accompanied by a serious risk of death. But the case has spurred a renewed interest in the potential of gene therapy as a tool to cure HIV.

Scientists have been eager to discover ways to genetically modify a patient’s own cells to mimic the delta-32 mutation. This would obviate the need to find donors who naturally have the mutation, which only occurs in roughly 1.5 percent of Caucasians. It might also remove the need for risky high-dose chemotherapy and irradiation. Writing in the August issue of Nature Biotechnology, two members of amfAR’s Research Consortium on HIV/AIDS Eradication (ARCHE), Drs. Steven Deeks and Mike McCune of the University of California at San Francisco, explore the progress that has been made in this area and what remains to be learned.

Deeks and McCune highlight a finding published in the same issue of the journal from researchers in California who genetically modified human stem cells. The researchers designed an enzyme called a zinc-finger nuclease to specifically target and destroy in the test tube the CCR5 gene present in the cells, leading to a state resembling the delta-32 mutation.  The cells were then infused into mice that had been rendered susceptible to HIV infection. When the mice were later challenged with HIV, they had lower levels of virus and maintained normal numbers of CD4+ T cells, the loss of which is a hallmark of AIDS.

As promising as these results were, many issues still need to be resolved. These mice were infected with HIV after the stem cell transplant, whereas humans would receive the transplant after HIV infection. Would the procedure still work under these conditions? If a patient received a transplant of cells depleted of CCR5, would the virus in their bodies be able to adjust and infect other susceptible cells in the body? Can sufficient numbers of cells be genetically modified to allow effective reconstitution of the immune system in the patient? Finally, is the procedure safe in the long term?

Despite those hurdles, “Now is not the time to stop” such research, concluded Deeks and McCune. “Antiretroviral drugs have intrinsic limitations that are unlikely to be surmounted,” they observe. “What is needed is a ‘game changer’ such as a cure for HIV infection.”

In addition to the cure-focused studies recently funded through ARCHE, amfAR is also supporting several projects involving gene therapy.

Dr. Johnston is amfAR’s vice president and director of research.