And three! After the patients in Berlin in 2009 and London in 2019, a third person has been cured of his infection with the AIDS virus. This 53-year-old man, followed in Düsseldorf, Germany, was infected in 2008. In 2013, sick with leukemia, he received a bone marrow transplant from a donor carrying a resistance mutation to infection. In 2018, after five years of follow-up, the medical team decided to suspend his antiretroviral treatments. Since then, no trace of the virus has been found in his tissues, and he is now in good health.
For Asier Saez-Cirion, researcher at the Institut Pasteur and member of the IciStem consortium, which aims to study these patients in remission, this new case of cure confirms researchers in their hope of soon achieving a definitive cure for people living with HIV. . Explanations.
L’Express: What do we know about this third case of probable recovery from HIV infection?
Asier Saez-Cirion: The therapeutic approach is broadly similar to that described for the patients in Berlin in 2009 and London in 2019. Each time they were people living with HIV, who developed leukemia. When the cancer no longer responded to chemotherapy, they needed a bone marrow transplant. When looking for a compatible donor, the medical teams were able to find a volunteer carrying a mutation in the gene coding for the CCR5 protein, the cell surface receptor that serves as an entry point for HIV. This mutation gives resistance to infection by the virus.
The first case of cure dates from 2009. How is it that there are only three patients cured in more than ten years?
In our study, we were able to identify around thirty people living with HIV who had received a bone marrow transplant. This is a risky procedure, in people who are already very sick, with unfortunately a high mortality rate. Among all these patients, there have been treatment failures: marrow transplantation very effectively eliminates infected cells from the body, but scientists realized that it was not enough. When the donor does not carry a mutation in the gene coding for the CCR5 molecule, the virus reappears fairly quickly. However, we are aware of two other patients transplanted from donors carrying the mutation. They are in an earlier stage of their follow-up, but they also seem to be on their way to recovery. However, it must be understood that this treatment cannot be offered on a large scale. It is a complex procedure, with the risk of complications, reactivation of opportunistic infections at the time of the transplant, or reactions of the new immune system against the patient’s body, with the need to take immunosuppressants. .
Did these cases of cure still make it possible to advance research on HIV?
With the Berlin patient, scientists realized that there might be a possibility of curing people with HIV. Until then, it was not very clear because it is a complicated virus, which is found in all tissues, with enormous diversity, an impact on the immune response, and which can stay in shape latent and escape all control mechanisms. This first patient was a catalyst, but remained anecdotal. The fact that this could have been repeated with the London patient showed that this may not have been a coincidence. There, with the case of Düsseldorf, we are beginning to talk about reproducing this result: this shows the way to a therapeutic strategy.
The key point is that you really need a double component. We must succeed in emptying the viral reservoir by decreasing the number of infected cells, as can be done with transplants. But doctors cannot analyze all the tissues and there may be some viruses hidden in the body. The mutation is therefore essential to prevent HIV from finding new targets to multiply. This means that the immune mechanisms must be optimized, either with new therapies or by introducing direct barriers such as this mutation in the gene coding for the CCR5 protein.
In addition, we are also interested in people who can maintain an undetectable viral load over a long period, by interrupting their antiretroviral treatments. This gives us perspectives on what it would be possible to reproduce in the medium term, so that people living with HIV can one day do without these drugs. We learn from all these cases to guide us towards a solution that would cure these people.
Where are these different works?
In their very early stages of clinical development. In the United States, a few teams have shown that it is possible to modify by gene therapy a small fraction of the cells preferentially targeted by the virus so that they no longer express this CCR5 protein on their surface. The results are quite promising because this modification on a very small population of cells already seems to have an effect on the level of viral infection. We can therefore think that by modifying a larger number of cells, we could indeed have a beneficial impact on the infection.
Why were they only able to target a very small number of cells?
For now, to achieve a proof of concept, scientists have extracted a few cells from the body, modified them in the laboratory and injected them back into the same person. With this technique, only a small part of the cells can be modified. But ultimately, the idea would be to develop a gene therapy treatment that could affect the entire immune system. For this, it would require a direct injection into the body, but for the moment we are not there yet, even if researchers are already working on it.
In addition, other approaches are being developed without going through gene therapy. This would mean, for example, reducing the number of infected cells, by targeting certain cellular characteristics known to be preferred by the virus to multiply. We already know some of them, because we know that these cells have specific nutrient needs, much like cancer cells. On the other hand, one can try to reinforce and optimize immune responses with molecules.
Are any of these avenues currently being explored by the Institut Pasteur?
We have already shown a few years ago that treatment started very soon after infection will have a positive impact on the possibility of controlling the virus, because we will both block the establishment of the reservoir and stimulate immune responses. We are currently starting a clinical trial where we will test immunotherapies in addition to conventional antiretroviral treatments. These are broad-spectrum HIV neutralizing monoclonal antibodies that will be administered during the acute phase of the infection. In phase 1 trials, these drugs have been shown to both block infection and promote more potent cytotoxic activities to eliminate infected cells. We hope that the combination of these immunotherapies and antiretrovirals administered in the early phase will make it possible to obtain both a smaller viral reservoir and a more effective immune response. After a year, we will stop the drugs, and we will study the ability of the included participants to control the virus. The objective is still to allow people living with HIV to permanently do without antiretrovirals.
Is the hope of achieving a definitive cure for the infection really there?
We’ve been talking about it for ten years. Several tracks have been launched, some have been abandoned but others are accelerating. We are coming to a time when the first clinical trials are really starting. In the next four or five years, we should begin to see the results, and to identify the strategy that will make it possible to induce a cure or at least a remission of the infection on a large scale in people living with HIV.
