With the help of a stem cell transplant, researchers have managed to cure an HIV patient with cancer of both diseases. This makes the “Düsseldorf patient” the third person in the world to be successfully cured of HIV. Ten years after the transplantation and four years after stopping the antiretroviral medication, there is still no detectable HI virus capable of replication in his cells. Although stem cell transplantation is not an option for HIV patients without cancer due to the serious side effects, the results are an important step on the way to curing HIV in other patients as well.
An infection with the human immunodeficiency virus HIV has so far been considered almost incurable. Antiretroviral drugs can slow down the multiplication of the virus to such an extent that patients with well-adjusted therapy have almost no viral load in their blood and do not develop any AIDS symptoms. But since the virus incorporates its own genetic material into the DNA of our immune cells, it has a permanent reservoir in the body. If the therapy is discontinued, it can therefore multiply again and, if left untreated, then lead to the full clinical picture of the deadly immune deficiency AIDS.
Stem cell donation with gene mutation
Researchers are now reporting for the third time worldwide that they have successfully cured an HIV patient. The 53-year-old man was diagnosed with HIV in 2008. Three years later he was also diagnosed with acute myeloid leukemia – a life-threatening form of blood cancer. If chemotherapy does not help, the last hope for those affected is a stem cell transplant. The patient’s own diseased bone marrow is destroyed by strong chemotherapy and radiation before receiving purified blood stem cells from a suitable donor.
The Düsseldorf patient also needed such a stem cell transplant, as reported by the supervising research team led by Björn-Erik Jensen from the University Hospital in Düsseldorf. “The aim of the transplantation was from the beginning to get both the leukemia and the HI virus under control,” says Jensen’s colleague Guido Kobbe, who carried out the transplantation. And indeed, a suitable stem cell donor with a genetic peculiarity was found: she carries a mutation in the CCR5 gene that ensures that the docking site for HIV on the immune cells is missing. Carriers of this so-called CCR5 delta32 mutation are therefore largely immune to HIV.
Transplant cures HIV
The attempt to cure an HIV-positive leukemia patient of both diseases at the same time by means of such a stem cell transplant was successful for the first time in 2007. The results were published in 2009 and the patient went down in medical history as the “Berlin patient”. In 2016, another patient, the “London Patient”, was cured of HIV and leukemia. Both men remained HIV negative after the transplant, even after stopping HIV medication.
In the case of the 53-year-old, who is now referred to as a “Düsseldorf patient”, the doctors treating him wanted to play it safe. Even after a successful transplant, he continued to take his HIV medication for almost six years. It was not until 2018 that he discontinued the therapy in consultation with the medical team. The researchers closely monitored his blood values and observed whether the HI virus multiplied again. They discovered traces of the HIV genome in individual samples, but observations over four years showed that the virus was no longer multiplying and there was also no immunological evidence of persisting HI viruses. “These are strong indications that HIV was indeed cured,” the researchers write.
Impetus for further research
Jensen’s colleague Tom Lüdde explains: “Our team decided to proceed very carefully and extremely thoroughly. Of course, the focus was on achieving the greatest possible benefit for our patients. In addition, it was also our goal to make a significant contribution to understanding the success factors of such a therapy.” To this end, the team documented the entire course in detail and thus also provides a unique basis for understanding the mechanisms of healing in detail.
“Following our intensive research, we can now confirm that it is fundamentally possible to stop the replication of the HI virus in the long term by combining two essential methods,” says Jensen. On the one hand, the virus reservoir in the patient’s immune cells must be largely emptied – in this case by destroying the patient’s own bone marrow. On the other hand, the HIV resistance of the donor’s immune system must then be transferred to the recipient, so that any remnants of the virus that may remain in the body have no chance of multiplying again. “Now we have to continue researching how this is possible outside of the tight framework conditions we have described,” says Jensen.
Therapy with serious side effects
For patients who are not already dependent on a stem cell donation, the previous procedure is out of the question: “A bone marrow transplant means a significant risk for the patient of serious, sometimes fatal side effects,” explains Boris Fehse from the University Hospital Hamburg-Eppendorf, who does not participate was involved in the study. “This risk is acceptable against the background of an inevitably fatal blood cancer, but not in the context of a disease that, like HIV infection, can be controlled today and is associated with a largely normal life expectancy in Germany.” In addition to the three success stories there are also several cases of patients who did not survive an appropriate therapy or in whom HIV persisted despite the transplantation because it switched to another receptor called CXCR4.
In the future, however, gene editing options could help improve therapy. Attempts to insert resistance into the patient’s own immune cells have so far met with little success, as there are still too many susceptible immune cells in the body. However, the precise documentation of the case of the Düsseldorf patient could help to find ways in which immune cells that have been made resistant can eliminate HIV reservoirs more effectively. “In summary, the very thoroughly processed case report from Düsseldorf underlines the fundamental potential of combined gene immunotherapies for the treatment of HIV infection, which should definitely be further investigated in larger clinical studies,” says Fehse.
Source: Björn-Erik Jensen (University Hospital Düsseldorf) et al., Nature Medicine, doi: 10.1038/s41591-023-02213-x