The remarkable research breakthrough that appears to have cured the anonymous “London Patient” of HIV is based on a stem cell transplant involving CCR5-delta 32 homozygous donor cells. This is the same treatment that cured Timothy Ray Brown, known as the “Berlin Patient” when he received two stem cell transplants in 2007 and 2008.
In 2009, Brown’s doctor, Berlin-based haematologist Gero Hütter, reported success (Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation: NEJM), and a decade on, the American recipient of his treatment remains HIV-free.
With the case of the London Patient, reported in Nature Tuesday, scientists have successfully duplicated Dr Hütter’s CCR5-delta 32 experiment from 13 years ago, with less pain than Brown, the pioneering survivor of HIV, had to endure.
Dr Hütter put Brown through an allogeneic stem cell transplant, which involved replacing his immune system with donor hematopoietic stem cells (usually found in bone marrow) so that his immune system could be regenerated, with no malignant cells. Importantly however, the donor he chose carried what is called a CCR5-delta 32 mutation.
On the surface membrane of immune cells is a protein called CCR5, which is, as a post on the Nature Education blog Scitable puts it, “like a door that allows HIV entrance into the cell”. However, about 1% of people of Northern European descent, mainly Swedes, are born with a mutation known as CCR5-delta 32, which “locks ‘the door’ which prevents HIV from entering into the cell”.
Simply put, HIV uses the CCR5 protein to enter immune cells, but it can’t latch on to cells that carry the delta 32 mutation. IciStem, a consortium of European scientists studying stem cell transplants to treat HIV infection, has a database of 22,000 donors with this HIV-resistant mutation.
IciStem scientists are tracking 38 HIV-infected people who have received bone-marrow transplants, including six from donors without the delta 32 mutation. The London Patient is 36 on that list; Number 19, the so-called “Düsseldorf Patient”, has been off anti-HIV drugs for four months now, The New York Times reported on Tuesday.
Incidentally, CCR5 is the protein that Chinese scientist He Jiankui claimed to have modified with CRISPR/Cas9 gene editing in at least two children in an attempt to make them resistant to HIV.