There are already four patients cured of HIV. The first of them was the American Timothy Ray Brown, known as the ‘Berlin patient’. He lived in this city when he was infected with the virus in 1995. In 2008 he stopped taking antiretrovirals and started to touch them again until his death in September 2020.
In 2016, another person with HIV stopped taking the drugs. It is about the ‘London patient’, who to this day continues without a trace of the virus in his body. Only a year later the ‘Dusseldorf patient’ and the ‘New York patient’ also stopped their medication. These last two cases have been released this year; the previous ones jumped to the media in 2011 and 2020.
It seems that HIV cures are starting to accumulate at an ever-increasing rate. This may give false hope to the nearly 40 million people living with the virus worldwide, more than a million of whom have been infected in the last year.
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because these cases are exceptional and cannot be generalized. Although they represent a milestone for science and open new avenues for virus research, there are several reasons why these cures will continue to be unique and ways must be found to end the global scourge of HIV by other means.
All four were cured because they underwent bone marrow transplants, a procedure in which stem cells that make immune cells are introduced into the patient. They are not infected with HIV and, in addition, they have a mutation in the CCR5 gene that inactivates it and confers resistance against the infection.
To do this, they first had to get rid of their own HIV-infected lymphocytes. They did this through chemotherapy, which knocked out the defenses of the four patients to leave them ready to receive the donated stem cells. But this procedure is not without risk: by erasing the immune system with a stroke of the pen, the entire body was left at the mercy of the slightest external attack.
strike down the fender factory
“It is a procedure that is not advisable to generalize,” he explains Eduardo Lopez Collazo, head of the group of the Innate Immunity Group of the Research Institute of Hospital La Paz, Idipaz. “The ‘factory’ of defense cells needs to be struck down and a new one installed. In this new one, a donor is sought who has the access door to HIV in their cells blocked,” he points out, but the process “is somewhat aggressive.” .
Javier Martinez Picado, ICREA researcher at IrsiCaixa, explains that the intervention is high risk. “Many people die from infections or graft-versus-host disease.is reserved for patients who are at risk of death and is not scalable to all people with HIV.”
Picado was part of the team that treated the ‘London patient’ and he says that this technique was used on other people who, unfortunately, died a few months later.
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Marrow transplantation is a procedure that has been used for more than forty years as a treatment for hematological cancers, which affect the circulatory systems of the human body (blood and lymph).
All four patients had these types of cancer. Therefore, the reason for bone marrow transplantation as a treatment option was not given for HIV but for tumors. This was a window of opportunity for research doctors, trying to kill two birds with one stone: treat leukemia and end HIV.
Not all that glitters is gold: the London patient died in September 2020 of aggravation of his leukemia. It ended up spreading to his brain and spinal cord, and five months later, he died at the age of 54.
For this reason, clinicians do not see this technique beyond an “anecdotal proof of concept,” he considers Vincent Estradaspecialist in infectious diseases at the Hospital Clínico San Carlos in Madrid.
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“Current drugs are so safe that any alternative would have to be very cheap, simple and without side effects,” he says. At present, patients lead a normal life by taking a single pill (which is actually several in one) daily, or injecting a drug every two months, “and we hope that soon it will be done every six.”
These drugs prevent the virus from replicating but the reservoirs remain intact. Therefore, he points out that, “from the conceptual point of view”, achieving healing is something very significant. “It’s so much better than having to take a pill.”
The cure for HIV, closer
Although this technique is not for all patients with HIV, it does open up the possibility of generalizing their cure in the future. This is what the Martínez-Picado team is working on: “We have already gone from observing a case to medical intervention, although it is high-risk. Now we are looking for a way to make it scalable.”
The goal is not to introduce donated immune cells but to modify those of the patient. Using apheresis, the CD4+ T lymphocytes are removed, the function of the CCR5 gene is disabled, and they are reintroduced. So there would be no incompatibility problems.Since finding a donor that is compatible with the patient and with the mutated gene is almost like looking for a needle in a haystack, “the probability is almost one in a million.”
Martínez-Picado points out that, once this milestone is achieved, the objective will be to scale up the technique to make it more affordable. “The Bill and Melinda Gates Foundation is making an effort to bring gene therapies to developing countries,” he recalls.
Beyond gene therapy, research on the cure of HIV goes through the “modulation of viral latency”, inactivating the DNA of the integrated virus in infected cells. There are also therapeutic vaccines and monoclonal antibodies, although recent setbacks have pushed that dream a little further away.
Vicente Estrada, for his part, acknowledges that his patients ask him every time news about HIV comes out. “But in the end the important thing is that whoever has HIV knows it, that it is correctly diagnosed, and to make sure that everyone takes their medication and is well.” With your feet on the ground.
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