Effectiveness of Bone Marrow Transplant in Suppressing HIV Creates Hope for Gene-Therapy Strategies in Treating Virus, Wall Street Journal Reports
The Wall Street Journal on Friday examined the case of an HIV-positive person who underwent a bone marrow transplant to treat leukemia and who has had undetectable HIV viral loads for almost two years. The procedure -- performed by German hematologist Gero Hutter of Berlin's Charite Medical University on a 42-year-old American living in the city -- "is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease," the Journal reports.
For the procedure, Hutter, who is not an HIV/AIDS specialist, replaced the patient's bone marrow cells with those from a donor with a naturally occurring gene mutation that provides immunity to almost all strains of HIV by preventing the CCR5 molecule from appearing on the surface of cells. According to the Journal, about 1% of Europeans, and even more in northern Europe, inherit the CCR5 mutation from both parents, and people of African, Asian and South American descent almost never carry it. Of 80 compatible blood donors living in Germany, Hutter's colleague Daniel Nowak found one who had inherited the mutation from both parents on the 61st sample he tested. According to the Journal, because immune-system cells are created in bone marrow, "transplanting mutant bone-marrow cells would render the patient immune to HIV into perpetuity, at least in theory."
The Journal reports that prior to the transplant, Hutter administered a standard regimen of powerful drugs and radiation to kill the patient's bone marrow cells and many immune-system cells, which may have helped the treatment succeed because the procedure killed many cells that harbor HIV. Transplant specialists then ordered the patient to stop taking his antiretroviral drugs when they transfused the donor cells because they were concerned that the drugs might undermine the cells' ability to survive in their new host. Although the plan was to resume the antiretroviral regimen once HIV re-emerged in the patient's blood, more than 600 days later, standard tests have not detected HIV in his blood, or in brain and rectal tissues where the virus often hides.
David Baltimore, who won a Nobel prize for his research on tumor viruses, said the case is "a very good sign" and a virtual "proof of principle" for gene-therapy approaches, but he cautioned that it could be a fluke. However, researchers who recently have reviewed the case believe that although it is likely that some HIV remains in the patient, it cannot "ignite a raging infection, most likely because its target cells are invulnerable mutants." According to the Journal, the researchers agreed that the patient is "functionally cured." Nevertheless, research has shown that blocking CCR5 can have fatal consequences, and bone-marrow transplants, which are given only to later-stage cancer patients, can result in death among 30% of patients. The Journal reports that although "scientists are drawing up research protocols to try this approach on other leukemia and lymphoma patients, they know it will never be widely used to treat AIDS because of the mortality risk."
Although re-engineering a patient's own cells through gene therapy could be a safer alternative, such strategies face "daunting technical challenges," the Journal reports. However, several research groups are testing different approach to treating HIV/AIDS, "[e]xpecting that gene therapy will eventually play a major role in medicine" (Schoofs, Wall Street Journal, 11/7).