It is the second case in history, and it represents a milestone in the search for effective treatment against HIV, although with some shortcomings. A second patient appears to be virus-free after receiving a stem cell transplant that replaced his white blood cells with HIV-resistant versions. However, the researchers caution that it is too early to say that they have been cured.
As published by Nature, the patient, whose identity has not been revealed, was able to stop taking antiretroviral drugs, with no signs of the virus returning 18 months later. The stem cell technique was first used a decade ago for Timothy Ray Brown, known as the “Berlin patient,” who is still virus-free.
Like Brown, this patient also suffered from blood cancer that did not respond to chemotherapy. It therefore required a bone marrow transplant, in which its blood cells would be destroyed and replaced with stem cells transplanted from a healthy donor.
But instead of choosing any suitable donor, the Cambridge University scientific team selected a donor who had two copies of a mutation in the CCR5 gene, which gives people resistance to HIV. This gene codes for a receptor found on the surface of white blood cells involved in the body’s immune response. Normally, HIV binds to these receptors and attacks cells, but a modification in the CCR5 gene prevents the receptors from working properly.
It is a very unusual feature, however: about 1% of people of European descent have two copies of this mutation and are resistant to HIV infection. But what is innovative about this trait is that it has been used as a therapy and, from the looks of it so far, it is effective.
Method
The researchers report that the transplant successfully replaced the patient’s white blood cells with the HIV-resistant variant. Cells circulating in the patient’s blood stopped expressing the CCR5 receptor and, in the laboratory, the researchers were unable to re-infect these cells with the patient’s version of HIV.
Eventually, the team discovered that the virus completely disappeared from the patient’s blood after the transplant. After 16 months, the patient stopped taking antiretroviral drugs , the standard treatment for HIV. At the last follow-up, 18 months after stopping the medication, there are still no signs of the virus. Success! Of course, it will take a little longer to determine if the patient is considered completely cured.
What are the shortcomings of this treatment?
Graham Cooke, a clinical researcher at Imperial College London, notes that this type of treatment would not be suitable for most people with HIV – who do not have cancer and therefore do not need a bone marrow transplant, a serious procedure that can sometimes have fatal complications. “If you are well, the risk of receiving a bone marrow transplant is much greater than the risk of continuing to take medications every day of your life,” he says, based on the fact that most people with HIV respond well to daily antiretroviral treatment.
However, Cooke adds that for those who need a transplant to treat leukemia or other diseases, it seems reasonable to try to find a donor with the CCR5 mutation, which would not add any risk to the procedure.
Gero Hütter, who led Brown’s treatment and is now medical director of stem cell company Cellex in Dresden, agrees that this type of treatment could only be used for a small group of patients. But he hopes the paper will stimulate renewed interest in investigating gene therapies targeting CCR5, which could be applied to a much broader group. “We are still waiting for the real breakthrough.”
