patient' is an HIV-positive man who developed acute myeloid leukaemia, received
successful treatment and subsequently experienced a relapse in 2007 that
required a transplant of stem cells.
Doctors chose stem cells from an individual who had an
unusual genetic profile: a mutation inherited from both parents that resulted
in CD4 cells that lacked the CCR5 receptor. This mutation, called CCR5 delta 32
homozygosity, is present in less than 1% of Caucasians in northern and western
Europe, and is associated with a reduced risk of becoming infected with HIV.
This is because all new infecting viruses need to use the
CCR5 receptor on CD4 cells when infecting an immune system cell of the CD4
Later in the course of HIV infection another type of virus
emerges that can use the CXCR4 receptor instead.
Before the stem cell transplant the patient received
chemotherapy treatment that destroyed most immune cells and total body
irradiation, and also received immunosuppressive drugs to prevent rejection of
the stem cells.
Antiretroviral therapy was halted on the day of the
transplant, and the patient had to receive a second stem cell transplant 13
days after the first one, due to a further relapse of leukaemia.
The patient continued to receive immunosuppressive treatment
to prevent rejection for 38 months, and at 5, 24 and 29 months post-transplant
colon biopsies were taken to investigate possible graft-versus-host disease in
the intestine. At each investigation additional samples were taken to check for
signs of HIV infection in the abundant immune cells of the gut wall.
During the 38 month follow-up period the donor CD4 cells
repopulated the mucosal immune system of the gut, to such an extent that the
frequency of CD4 cells was almost twice as high as in HIV-negative healthy
controls, and this phenomenon was also seen in a control group of ten
HIV-negative individuals who received stem cell transfers.
The repopulation of CD4 cells was accompanied by the
complete disappearance of host CD4 cells, and after two years the patient had
the CD4 count of a healthy adult of the same age.
One of the challenges for any approach to curing HIV
infection is long-lived immune system cells, which need to be cleared before a
patient can be cured. In the case of the Berlin
patient CCR5-bearing macrophages could not be detected after 38 months, suggesting that
chemotherapy had destroyed these longer-lived cells, and that they had also
been replaced by donor cells.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
The patient did not resume antiretroviral therapy after the
Nevertheless HIV remained undetectable by both viral load
testing (RNA) and tests for viral DNA within cells, and HIV antibody levels
declined to the point that the patient has no antibody reactivity to HIV core
antibodies, and only very low levels of antibodies to the HIV envelope
Seventeen months after the transplant the patient developed
a neurological condition, which required a brain biopsy and lumbar puncture to
sample the cerebrospinal fluid for diagnostic purposes. HIV was also
undetectable in the brain and the CSF.
An additional indication that HIV is not present lies in the
fact that the patient’s CD4 cells are vulnerable to infection with virus that
targets the CXCR4 receptor. If any virus with this preference was still
present, the researchers argue, it would be able to swiftly infect the large
population of memory CD4 cells that has emerged.