A man, known as the patient from Dusseldorfbecomes the third case of healing HIV infection in the world, after receiving a stem cell transplant to treat his myeloid leukemia. Four years after having undergone the transplant, and despite the interruption of antiretroviral therapy against HIV, the patient remains free of the virus, as detailed in a study recently published in the scientific journal Nature Medicine.
The researchers have detected neither viral particles nor any increase in the immune response against HIV in this person’s body for 44 months, and they have also ruled out the presence of a viral reservoir, responsible for the disease becoming chronic, for what they consider to be the case of patient from Dusseldorf is a case new healing.
The study of this case has been carried out by scientists from the iciStem consortiumcoordinated by the IrsiCaixa AIDS Research Institute and the University Medical Center of Utrecht (Netherlands). Javier Martinez-Picado, ICREA researcher at IrsiCaixa, co-director of IciStem, and co-author of the article explained: “Together with an excellent team of professionals from all over the world, we have spent nine years studying these exceptional cases in which, thanks to a therapeutic strategy, the virus remains totally removed from the body. We want to understand each step of the healing process in detail to be able to design strategies that are replicable for the entire population.”
How the Düsseldorf patient was cured of HIV
The man who would later be known as the patient from Dusseldorf He was diagnosed with HIV infection in 2008, and began antiretroviral treatment with which he managed to control the infection and the presence of the virus decreased to undetectable levels in the blood. In 2012 developed leukemiawhich is a cancer that attacks cells of the immune system and which he was treated with a bone marrow stem cell transplant in 2013.
“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 go through a transplant”
To carry out the transplant, a stem cell donor is sought who is a carrier of the CCR5Δ32 mutation, a genetic alteration that prevents one of HIV’s entry pathways into cells from occurring, making it more difficult for the virus to infect them. As he points out, José Alcamí, virologist and director of the AIDS Immunopathology Unit of the Carlos III Health Institute, who did not participate in this study, “Like the so-called London and Berlin patients, the transplant was done with cells from a donor who carry a genetic deletion in one of the major HIV recipients, so the cells are resistant to infection.” Mary SalgadoIGTP researcher at IrsiCaixa and co-author of the study, explains that “it is very complicated for all these factors to coincide, only 1% of the population has this mutation and, in addition, it is necessary to be a blood-compatible donor to avoid rejection of the transplant”.
Although the patient suffered two relapses of leukemia and several complications, more than five years after receiving the transplant he finally stabilized and researchers decided to stop giving him antiretroviral treatment for HIV. Currently, the man is 53 years old and his health is good. “When he stopped taking the treatment, we followed him up for 44 months and we did not detect any trace of the virus in the patient’s blood or tissues,” says Salgado. “We have also not seen any immune response characteristic of a viral outbreak. Their defenses are not activated against HIV because they do not have to defend themselves against the virus.
Other cases of HIV cure or remission of the virus
The authors of the study rely on their results to affirm that their patient has been cured of HIV infection, but it is not the first case, since the Berlin patients and London They were the pioneers in this scientific milestone, and although they are the only cases in which it is possible to speak of a cure, HIV remission has been confirmed in two other patients: the one in New York and the one at the City of Hope Hospital located in Duarte.
“None of them have special immune characteristics that allow them to control HIV infection spontaneously, rather the virus has been eliminated from the body as a result of medical intervention. This differentiates these cases of eradication from those of functional healing 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”, Salgado details.
He patient from Dusseldorf demonstrates for the third time that there is a possibility of curing HIV, but it is important to remember that stem cell transplantation is a very aggressive therapy with many side effects, which is why it is only used to combat hematological diseases in patients who lack other alternatives, while people with HIV do have an effective therapy at their disposal: 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 go through a transplant”, comments Martínez-Picado.
On what implications it has in daily practice, Alcamí, who did not participate in the study, believes that despite the fact that “like all the cases of eradication or functional cure that we publish, they are exceptional cases that cannot be extended to practically all of the patients. It is unethical to perform a bone marrow transplant if it is not indicated by a hematological disease because the mortality of the procedure is very high (>40%). Achieving this effect with gene therapy –deleting the CCR5 gene in progenitor cells or CD4 lymphocytes– as is always discussed and suggested by the authors in the last paragraph, is still a distant goal. Trials carried out to date have given very transitory results with no clinical relevance. This is important to highlight.”