More than 15 years without HIV and without medication: a patient from Barcelona opens a path for the functional cure of AIDS

A Spanish woman with HIV has been controlling the virus spontaneously for more than 15 years, without taking medication and with an undetectable viral load, in a case that has been presented as "unique" and "exceptional" of functional cure of the disease.

The study of this patient —whose identity or age have not been disclosed to protect her anonymity— has been carried out by a team led by doctors from the Hospital Clínic de Barcelona, ​​and will be presented this week at the 24th edition of the Conference AIDS International in Montreal (Canada).

“This lady has been without medication for more than 15 years.

After spending a short period of time with her, she totally controls the AIDS virus and this has a very important aspect: we have been able to find out what is the possible mechanism that allows it”,

HIV infection is a pandemic that affects nearly 38 million people.

AIDS – the most advanced stage of the infection – kills 650,000 patients each year.

Four decades of scientific advances have managed to save millions of infected people thanks to antiretroviral therapy (ARV), a cocktail of drugs that prevents the replication of the virus to the point of making the viral load undetectable and, therefore, untransmittable.

This is the only treatment available for the vast majority of carriers of this virus that destroys the immune system.

Currently, more than 28

Millions of HIV-positive people can lead a normal and quality life thanks to the daily intake of a pill.

However, a definitive cure has not yet been found.

Although antiretrovirals are effective in suppressing viral replication, HIV persists in reservoirs and recovers after discontinuation of therapy.

There are very few exceptions: a few people who are called "aftercare controllers" are able to keep the virus at bay after the medication is withdrawn.

In addition, there are also the so-called "elite controllers" who achieve the same thing despite not having started antiretroviral therapy.

These are also rare: less than 1% of those infected.

The one already baptized as "patient from Barcelona", however, does not belong to these two groups, since she was diagnosed in 2006, already with an acute infection, something that is not typical of either of them.

This woman was included in a clinical trial directed by José M. Miró

whose objective was to know if the immune system could be reinforced so that it controlled viral replication.

Of a cohort of patients, one group received antiretrovirals alone and the other received a series of additional immunomodulatory treatments, including an immunosuppressant, cyclosporine A. HIV in plasma”, describes Dr. Núria Climent, a researcher with the AIDS and HIV infection group at the August Pi i Sunyer Biomedical Research Institute (Idibaps), during an interview between several members of the medical team and EL PAÍS.

In fact, this woman was the only one of the 20 individuals who reacted like this.

She “she did not rebound the virus, and she has not rebounded for 15 years and more than 50

viral load tests;

not that he could have any small, low-level presence at times.

It has always been undetectable”, Miró completes.

Once the immunological reaction of this patient was discovered, the next step was to infect the CD4+ T lymphocytes, which are the main target of HIV.

And it was found that these were capable of replicating the virus, which suggested that there was no problem in its entry into the CD4+ T lymphocytes.

On the other hand, when Climent and Sonsoles Sánchez Palomino, another team doctor, carried out cultures with other subpopulations of blood cells, they found that there was a very drastic control of virus replication.

“This suggested that these other subpopulations were the ones involved.

tests

we showed that they were the cells called

[NK, or “natural killers” in Spanish] and also CD8+ T lymphocytes″, describes Dr. Sonsoles Sánchez-Palomino.

These NK cells are the ones that our body uses to trigger an immune reaction when it comes into contact with the AIDS virus and, if it is powerful, it can control it.

It is as if we were witnessing for the first time the unmitigated victory of the immune system over the virus

Josep Mallolas, doctor

The great novelty of this research is that it has been possible to characterize which subpopulations of NK and which subpopulations of CD8+ T lymphocytes are the ones that could be involved in this phenomenon: they are NK cells that have memory and also others called T Gamma-Delta , and are the ones that provide innate immunity.

"The patient has very high levels of both and could be blocking or destroying those that are infected," describes Dr. Climent.

The Barcelona patient is unique not only because there are very few people with HIV control so many years after stopping treatment, but also because the control mechanism has been characterized, and it is different from that of elite controllers. something that opens new ways to boost the activity of those promising NK and Gamma Delta cells.

"If we were able, through treatment, to repeat or replicate that innate immune capacity that this woman has, the advantages would be enormous," Dr. Mallolas celebrated during the video call.

The medical team also discovered, over time, that there was a "very pronounced and progressive" drop in the number of viruses in the reservoir.

“It is as if we were witnessing the unmitigated victory of the immune system over the virus for the first time.

It is beautiful to see how the viral reservoir is getting smaller, it is as if the NK had the virus cornered.

And they are eliminating more and more infected cells.

Probably, there will come a time when the reservoir reaches zero”, added the head of the HIV unit at the Clinic.

Functional healing, not definitive

The researchers emphasize that the patient from Barcelona has a functional cure, that is, that without any type of treatment it controls the replication of HIV, but it is not that it does not exist: when her cells are analyzed, there is a viable virus capable of causing new infections .

For this reason, his is a different case from that of the media patients in London and Berlin, individuals who completely eliminated it from their body thanks to a bone marrow transplant.

Doctor Juan Ambrosioni, doctor of the HIV-AIDS unit of the Clinic,

stresses that this measure is so aggressive that it cannot be extrapolated to other patients.

“You can't use it for the almost 40 million people with HIV.

On the other hand, if you manage to detect a group with a certain genetic substrate that through certain interventions can spontaneously control the virus, you would be doing something potentially much easier to scale."

Next steps

The next step in this research is to identify exactly what combination of factors specific to the patient along with those that Dr. Miró administered to her in the clinical trial led to this control of the virus in her, but not in the rest of the participants.

The final idea is to replicate the conditions that this woman represents in other people who, a priori, do not have them.

“What is very important is to study this lady in depth and that, once we know her cells and her immunity 100%, we are capable of designing research projects for others, in such a way that although we cannot cure them, we manage to that they may be without treatment, with an undetectable viral load and without the possibility of being contagious for many years.

Now a fascinating range of research possibilities is opening up”, Mallolas reflected.

One of the next lines of research is to analyze the rest of the clinical trial cohort to see what the Barcelona patient has compared to the other nine participants who were treated with the same.

"This cohort is going to give us a lot of information about whether the treatment did something special to her and not to the others, or if it did it to everyone and they only needed to have certain genetic factors to trigger it," says Dr. Climent.

Researchers from the Hospital Clínic-IDIBAPS/University of Barcelona, ​​the Infectious Diseases Network Biomedical Research Center (CIBERINFEC), the Germans Trias i Pujol Hospital and the Carlos III Health Institute have participated in the follow-up of the case and the study.

In the best of cases, this team aspires to achieve a definitive cure for the woman if the reservoir of the virus falls even further, as it has been doing for the last 15 years.

At worst, she could need antiretroviral therapy again.

“You have to be very careful, we could have 15 years of success, but not 16”, Mallolas warned.

The fact of advanced age can also be a negative factor, as Dr. Climent warns that they do not know how aging can affect five or ten years from now,

Little is known about the patient from Barcelona, ​​beyond the fact that she is a woman and that she is already "a certain age", according to the description of the researchers, since she has requested to remain anonymous.

It is also known that she is in excellent health, and that her immune system and tests are perfectly normal.

Mallolas describes her as a person who has given "everything" for science.

“She is a super collaborator and this is to be appreciated”, she praised, “because there are many volunteers in the world of HIV who go unnoticed and who are, however, the ones who allow studies like this to be carried out”.

You can follow