Josep María Miró, infectologist: "Let's see if we can induce cells that suppress HIV in other patients"

The researchers at the Hospital Clínic de Barcelona know that they have a unique case, pure gold, on their hands. A woman has been able to overcome HIV after suffering the acute phase of the infection without taking medication. The patient's immune system has reacted in a unique way to present a "functional cure" for 15 years. The virus is in her body, but at very low levels. There is no disease.

The team of toilets has not known until now what has been the mechanism that has achieved this global phenomenon. One of its members, Dr. Josep María Miró, from the Clínic's infectious disease service, tells in this interview how this successful microscopic battle works, the journeys they have followed to corroborate what the analytics showed and the "optimistic" implications that may have for the future of millions of people who are still living with this pandemic.

After 15 years of monitoring this patient, it is now that they have managed to find out how she does it.

It is the most important part of the case. This lady entered the study in 2006 and has been undetectable for 15 years [el virus no aparece en las analíticas] and now it has been possible to know the mechanism by which the virus is in the body, but at undetectable levels in the blood and tissues.

What is that mechanism?

She has a very powerful innate immune response against the virus. Basically there are two types of cells. The Natural Killers, natural killers, who are known as NK. And other lymphocytes that are called Gamma-Delta. The conjunction of these responses is what makes the levels of the virus in this lady undetectable.

It is very important because it allows detecting an exquisite control mechanism for 15 years. It remains to be seen whether the treatment he received in his day or other treatments can induce these cells, which could benefit other people infected with HIV.

Does this person have a super immune system or is there a correlation with the treatment they followed 15 years ago?

This is what we are analyzing. We're looking at the other people who were in your treatment arm retrospectively and testing those samples to see if they've developed a similar immune response. We also see if this person has some kind of favorable genetic profile so that he could develop that immunity.

What have they discovered?

This case is different and it is new because, although there is a very small group of people – less than 1% – who do not need treatment for HIV, it is not what has happened with this woman. That group is known as elite controllers and since they are infected they present very low virus levels. In addition, they have a favorable genetic profile and a very powerful adaptive response.

However, she did have an acute phase of the infection.

Yes. He developed an acute HIV infection. He presented high fever, malaise, adenopathies... He came to have infections of the neck and esophagus. It doesn't have a genetic profile like elite controllers and it didn't have that adaptive immune response. He had a serious illness and was treated with antiretrovirals and drugs to stimulate the immune response. And already at the first control stop its particularity was detected.

Why do they stop the treatment?

It is the cotton test: the system is reinforced and the treatment is stopped to see if the virus rebounds or if, at least, it rebounds at low levels. Well, all the patients in her group bounced, but she didn't. At the first stop she didn't, so we began to follow her very carefully. After 15 years and 50 viral load determinations, it has remained undetectable. And now, thanks to advances in immunology and virology, we have been able to determine its mechanism. Before, we didn't have the tools.

I imagine that when they saw the analysis they would rub their eyes. And then even more.

Of course. At first we did other things to corroborate. We saw if we could get the virus from her cells and tissues to check that she was infected, since she had a detectable load early on. And we verified that, by stimulating her cells, we easily obtained the virus. We then sequenced this virus to see if it was complete or if it was missing something that would make it more easily controllable. And it was a complete virus. It was not missing anything and was able to infect other cells in the laboratory. Now, by adding control cells to that virus, even if we stimulate its viral reservoir, it cannot infect cells in the laboratory.

The verification is complete.

We have the double test: the person and the laboratory where, even stimulating cells with the virus, if we add those NK and GD, the virus remains asleep inside them. The immune response is characterized by these two types of cells.

What does this finding mean for the rest of the patients?

It can open some very interesting doors. We know of another virus control mechanism. We are going to see if we can induce these types of cells and other patients can suppress the replication of their viruses. If we could reproduce it, it would open many doors because it would have a very important applicability for many people.

Will you avoid those treatments for life that must be followed today?

Current treatments are very fortunate and increasingly accessible. Patients have suppressed virus and do not transmit it. But taking a treatment for life can lead to its complications due to problems with toxicities or the vital circumstances of the same people who go through different moods or encounter the impossibility of access to medicines and the virus, then, it can rebound, infect and progress the disease. That is why it is good to be able to control the virus and to know if we can generate this type of cells in other people.

The ONU has warned this week that COVID-19 has allowed HIV to regain momentumWhat is your analysis?

COVID has negatively impacted many diseases, not just infectious ones. The diagnosis and treatment of other pathologies has worsened, but it is different in developed or developing countries. There has been a global impact, but uneven. Countries with more resources have been affected less and others much more. In sub-Saharan Africa and South America the number of new cases and deaths from HIV has increased after many years of decline.

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