The call ‘patient from Dusseldorf‘, a 53-year-old man is the third patient in the world to be completely cured of HIV through a stem cell transplant. As in the case of the other two patients (Patient from Berlin and Patient from London), the transplant was performed to treat an acute haematological disease, which had developed in addition to the HIV infection.
The study published in “Nature Medicine” was carried out by the international consortium IciStem, coordinated by the IrsiCaixa AIDS Research Institute and the University Medical Center of Utrecht (Netherlands). «For 9 years we have been studying these exceptional cases in which, thanks to a therapeutic strategy, the virus is completely eliminated from the body. We want to understand each step of the curing process in detail to be able to design strategies that are replicable for the entire population”, explains Javier Martínez-Picado, ICREA researcher at IrsiCaixa, co-director of IciStem, and co-author of the article.
The first was Timothy Brown, known as “the Berlin patient”, who died in September 2020 from cancer. Then followed the London patient, Adam Castillejoand now from Düsseldorf, a 52-year-old man who for the moment prefers to remain anonymous.
Brown spent more than 12 years without a trace of HIV. Now, coinciding with the Conference on Retroviruses and Opportunistic Diseases (CROI), we present the data of this person who, almost 10 years after stem cell transplantation from an unrelated donor and more than 4 years after finishing therapy against HIV, you are free of the virus. In fact, he explains ABC Health María Salgado, IGTP researcher at IrsiCaixa and co-author of the study, “does not have anti-HIV antibodies; that is, it is as if he had never been infected with HIV.
The fact that the virus has not reappeared is the result of extremely meticulous scientific and therapeutic preparation and monitoring. To date, this is the longest and most accurate diagnostic follow-up of a patient with HIV after a stem cell transplant.
Now he qualifies, Salgado qualifies, due to the risks involved, stem cell transplantation is only performed in the framework of the treatment of other potentially fatal diseases.
In 2008, the patient was diagnosed with HIV. After the diagnosis, he started antiretroviral treatment, which allowed him to control the infection and reduce the amount of virus to undetectable levels in his blood.
Six months after starting his HIV therapy, he was diagnosed with acute myeloid leukemia (AML), a potentially deadly type of blood cancer. In 2013 she underwent a stem cell transplant for this disease. “From the beginning, the goal was to treat both leukemia and HIV,” explains hematologist Guido Kobbe, who performed the transplant in Düsseldorf.
He does not have anti-HIV antibodies; that is, it is as if he had never been infected with HIV
Mary Salgado
IGTP researcher at IrsiCaixa
Stem cells taken from the donor had a specific mutation in the CCR5 gene (CCR5Delta32 mutation). This rare genetic mutation, which is prevalent in central and northern Europe, results in the absence of a binding site for HIV on immune cells, providing good protection against HIV infection. Stem cell transplantation thus treated both diseases. This genetic alteration prevents you from producing one of the entry doors for HIV into cells and, therefore, makes infection more difficult.
«That all these factors coincide is very complicated, only 1% of the population has this mutation and, in addition, it is necessary that it be a compatible donor at the blood level to avoid rejection of the transplant, ”says Salgado.
In 2018, anti-HIV therapy came to an end, which had guaranteed control of any remaining HIV until then.
To ensure that one could ultimately speak of a cure, extensive tests were carried out throughout this period, for example to determine whether signs of replication-capable HIV virus could still be found.
In ‘Nature Medicine’, the authors describe what additional indicators they reviewed to be able to exclude any remaining active HIV infection and thus now assume cure after stem cell transplantation.
The Dusseldorf patient is a third proof of concept showing that there is a possibility of curing HIV
«We can confirm that it is possible to sustainably prevent HIV replication by combining two key methods. On the one hand, we have the extensive depletion of the virus reservoir in long-lived immune cells, and on the other, the transfer of HIV resistance from the donor’s immune system to the recipient, ensuring that the virus has no chance to spread again. », details Björn Jensen, from Düsseldorf University Hospital.
The confirmation of the healing of the patients in Berlin and London precedes that of the Dusseldorf. Although these are the only three cases in which one can speak of a cure, the remission of HIV in two other patients has already been presented at scientific conferences, acknowledges María Salgado. They are the patient from New York and the one from the City of Hope Hospital.
But, as Salgado states, “none of them have special immune characteristics that allow them to control the HIV infection spontaneously, rather the virus has been eliminated from the body as a result of a medical intervention. This differentiates these cases of eradication from those of functional cure in elite controllers or post-treatment achieved so far, in which people’s own bodies had special factors that allowed them to control the virus.
The Dusseldorf patient is, therefore, a third proof of concept that demonstrates that there is a possibility of curing HIV and ignites, once again, the hope of the scientific world.
not scalable
However, the researcher warns, this strategy is very aggressive and is not scalable to the rest of the population. Stem cell transplantation is only used for people who suffer from a hematological disease and have no therapeutic alternative.
In the case of people with HIV, there is an alternative, and it is antiretroviral treatment. “A possible strategy that is already being worked on is to introduce the CCR5Δ32 mutation through gene therapy to achieve a cure for HIV without having to undergo a transplant,” adds Martínez-Picado.