Doctors who carried out a stem cell transplant on an HIV-infected man with leukaemia in 2007 say they now believe the man to have been cured of HIV infection as a result of the treatment, which introduced stem cells which happened to be resistant to HIV infection.
The man received bone marrow from a donor who had natural resistance to HIV infection; this was due to a genetic profile which led to the CCR5 co-receptor being absent from his cells. The most common variety of HIV uses CCR5 as its ‘docking station’, attaching to it in order to enter and infect CD4 cells, and people with this mutation are almost completely protected against infection.
The case was first reported at the 2008 Conference on Retroviruses and Opportunistic Infections in Boston, and Berlin doctors subsequently published a detailed case history in the New England Journal of Medicine in February 2009.
They have now published a follow-up report in the journal Blood, arguing that based on the results of extensive tests, “It is reasonable to conclude that cure of HIV infection has been achieved in this patient.”
If a cure has been achieved in this patient, it points the way towards attempts to develop a cure for HIV infection through genetically engineered stem cells.
The German researchers and San Francisco-based immunologist Professor Jay Levy believe that the findings point to the importance of suppressing the production of CCR5-bearing cells, either through transplants or gene therapy.
Scientists were sufficiently intrigued by the Berlin patient that they met in Berlin in 2009 to discuss how they could coordinate efforts to identify CCR5-delta32 homozygous donors and expand the supply of stem cells from these donors, for example through sampling blood cells from the umbilical cord of babies born to mothers who are homozygous for CCR5-delta32, in order to eventually facilitate stem-cell therapy.
Gene therapy techniques which can transform stem cells – and all their descendents – into cells resistant to HIV entry may be a more practical option than looking for matching donors.
Several US research groups announced in October 2009 that they had received funding to explore techniques for engineering and introducing CCR5-deficient stem cells.
If these approaches prove successful they will be expensive, so in the early stages it is likely that they would be reserved for people with no remaining treatment options or a cancer requiring bone marrow or stem cell transfer.
As Timothy Brown’s experience shows, curing HIV infection through ablative chemotherapy, immunosuppressive drugs and stem cell transfer is not a course of treatment for the faint-hearted. It has required courage, determination and a lot of support to become the first person to be pronounced `cured` of HIV infection.
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