In 2010, doctors presented to the world the case of Timothy Ray Brough, since then known as the “Berlin Patient,” the first person in the world considered cured of HIV. After a stem cell transplant from a donor who had the CCR5-Δ32 mutation, which prevents HIV from entering cells, the virus disappeared from his body.
A decade and a half later, Christian Gaebler’s team at the Charité Hospital reported a new case of HIV-1 remission with this regimen, which doctors called the “second Berlin patient.” Although this is the seventh patient reported to have been cured of HIV so far, his case is very special: while the previous patients received cells that were homozygous (with two copies of the gene that encodes CCR5), in this new case the donor was heterozygous and only one of the two copies contained the mutation.
Expanding alternatives
According to the authors, who presented details of the case in an article published Monday in the magazine natureThe patient is a 60-year-old man from Berlin, who was diagnosed with HIV in 2009 and developed acute myeloid leukemia in 2015. The patient underwent an allogeneic stem cell transplant to treat the cancer, although a CCR5 Δ32 homozygous donor could not be found. However, three years after transplantation from a heterozygous donor, the patient discontinued antiretroviral therapy and no evidence of HIV-1 recurrence was found six years after transplantation.
These results provide further evidence that the presence of cells without CCR5 expression is not a prerequisite for achieving HIV-1 remission after stem cell transplantation.
The researchers believe this finding expands the alternatives available for this specific type of patient, HIV carriers whose cancer requires a bone marrow transplant. These results provide further evidence that the presence of cells without CCR5 expression is not a prerequisite for achieving HIV-1 remission after stem cell transplantation. Recently, a case (the so-called “Geneva patient”) was reported in which remission was achieved using stem cells from a donor without the CCR5Δ32 mutation, suggesting that – although facilitated – it would not be necessary to achieve remission.
Interesting exceptions
Javier Martínez Picado, ICREA Research Professor at the AIDS Research Institute IrsiCaixa, warns that this type of medical intervention is exclusively for people with severe blood diseases, but alternative strategies are being worked on. He explains to SMC that there is heterozygosity rather than homozygosity, “making it closer to the Geneva case that we published last year within the IciStem group, where donors and recipients completely lacked the mutation and which is also currently in remission.”
This is excellent work, agrees Julia Blanco, head of the Virology and Cellular Immunology Group at the Ersi Caisha Institute for AIDS Research. In his opinion, the study provides two important pieces of information regarding other previously reported cases. “First of all, this case confirms that there is no need for a donor lacking the HIV coreceptor CCR5,” he told SMC. “Second, the authors suggest an important role for the presence of protective antibodies (neutralizing and ADCC mediators) at the time of transplantation. This is the first time this phenomenon has been described.”
Although these patients constitute important proof of concept that HIV infection can be eradicated, they are not generalizable cases.
Josep Malolas
— Head of the HIV and AIDS Unit at Hospital Clinic Barcelona
“It is very good work and has an important impact,” adds Josep Malolas, head of the HIV and AIDS unit at Hospital Clínic Barcelona. “Among the reported cases, almost all except Geneva patient “They had the delta 32 mutation. This and the heterozygote that has been published now are the exception, although the important thing is that they open the door to these transplants without the donor being homozygous delta 32,” he says.
However, for Malula there are also very important limitations. “Although these patients represent an important proof of concept that HIV infection can be eliminated, they are not generalizable cases,” he stresses to SMC. “They are all patients with a tumor, usually a blood disease, and undergoing very aggressive treatments whose complications can sometimes be fatal. It would not be logical or ethical to subject a patient to these very aggressive treatments if he did not have an underlying serious tumor.”