Timothy Ray Brown, also known as the Berlin patient, is the only patient to every be “cured” of HIV infection. Mr. Brown announced the establishment of the Timothy Ray Brown Foundation on July 24, 2012 at the International AIDS Conference in Washington D.C. The goal of the foundation is to support researchers in their efforts to find a cure for HIV infection. Years after he was diagnosed with HIV infection, Mr. Brown has remained HIV free as a result of the treatment that he received while living in Berlin, Germany. In 1995, he was first diagnosed with HIV infection and was successfully treated with highly active antiretroviral therapy (HAART). While living in Berlin in 2007, he was subsequently diagnosed with acute myeloid leukemia (AML). Despite receiving two courses of induction chemotherapy followed by one course of consolidation chemotherapy, he had a relapse of this leukemia. His oncologists recommended allogeneic stem cell bone marrow transplantation as the next treatment option. Due to his HIV infection, his oncologists searched for an HLA matched bone marrow donor that also had a mutation in the CCR5 receptor termed delta32/delta32. This specific mutation prevents some forms of HIV1 viruses from infecting CD4 lymphocytes. After successful engraftment of the allogeneic stem cell bone marrow transplantation, it was found that the Berlin patient had a functional cure for his HIV infection. His leukemia relapsed yet again, and he received a second bone marrow transplant, but has since been free of both leukemia and HIV infection.
This is a miraculous story… but exactly how does the CCR5 delta32/delta32 mutation confer resistance to HIV infection?
The HIV1 virus attacks the body’s immune system by infecting CD4 helper lymphocytes. As the immune system is weakened, patients can develop opportunistic infections (termed Acquired Immunodeficiency Syndrome, AIDS) that normally would not develop in an immuno-competent person. In order to infect and enter CD4 helper lymphocytes the virus must bind to the CD4 molecule on the cell surface along with a second cell surface co-receptor. That second cell surface co-receptor can be either CCR5 or the CXCR4 receptor. About 1 percent of the Caucasian population has a mutant CCR5 receptor that has a 32 base deletion that prevents the HIV virus from binding to it and thus prevents infection by the HIV virus. Fortunately for Mr. Brown, his oncologists in Berlin, Germany were able to find a HLA matched donor that also had the delta32/delta32 mutation in the CCR5 receptor. After successful engraftment of the transplanted bone marrow stem cells, Mr. Brown was both “cured” of his leukemia and the HIV infection. Although he has sustained some neurological complications from the treatment, Mr. Brown was able to stop his HIV medication and he has been in complete remission from the leukemia.
This is quite a remarkable example of how modern day science and medicine can find a cure for disease. It is important to note that this type of treatment is not broadly applicable to the general population. This is due to the fact that bone marrow donors need to be HLA matched to the recipient and in the case of HIV infection would also need to have the CCR5 co-receptor mutation. Since this mutation occurs at only 1% in the white population, the probability is low that a donor with the correct HLA match and the CCR5 mutation would be found for HIV infected recipients. In addition, it should also be noted that stem cell bone marrow transplantation is a very toxic and morbid procedure and can result in the death of the recipient. Despite this, the fact that medical scientists were able to accomplish such a cure gives hope that future research may eventually lead to a more broadly applicable treatment that can result in a cure for more HIV patients.
See the CBS news report about the Berlin patient that aired on the 30th anniversary of the discover of the HIV virus:
Gero Hutter et al. “Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation” N Engl J Med 2009; 360: 692-698.
Image: CDC, C. Goldsmith