Florence Cunzolo
03/05/2021 12:11 AM
Clarín.com
Good Life
Updated 03/05/2021 12:11 AM
It was during a regular medical pass, while discussing cases of different patients, when infectologists Analía Urueña and Isabel Cassetti were convinced that they were facing a
totally different one
.
It was a woman with HIV, who had debuted with advanced disease (AIDS) and who, after suspending the treatment followed for a decade, did not experience a rebound in viral load.
After more than 12 years without medication, almost no traces of virus are found in his body, to the point that he
no longer has antibodies against HIV, his test today is negative
.
The "Patient from Buenos Aires" is a unique case worldwide, studied in depth between Argentina and the United States, for which there is still no explanation.
Weight loss, blurred vision, weakness on the left side of the body and fever were the symptoms that led her to the consultation in 1996. At the Naval Hospital, where she was admitted, she was
tested for HIV and she was positive
.
In addition, due to his neurological symptoms, a brain MRI was indicated, which showed lesions compatible with the infection, which were subjected to biopsies.
The condition of the woman, now 56 years old, was advanced: her CD4 lymphocyte count, key players in the immune system, was very low, so
her defenses were weakened
.
She started antiretroviral treatment (ART) with three drugs and evolved favorably, after which she was discharged.
In 1997 she began to be treated at Helios Salud, she was one of the first patients of the institution.
"I met her in 2005, when she replaced the doctor who attended her. She had quite a lot of
toxicity from the medication
, mainly lipodystrophy, a fat distribution disorder (which was very common with the old antiretrovirals) and quite marked dyslipidaemia, she was She was very tired of taking the tablets that were very bad for her and, in turn, she took them quite badly. Despite that, her viral load was undetectable, but we know that this can fail over time and end up generating resistance ", says Analía Urueña.
Efforts to improve adherence to treatment were unsuccessful so, due to the adverse effects it presented, in 2007 they decided to
suspend the medication on
a
scheduled basis
.
Important clarification: such behavior is not currently recommended, doctors warn.
"In the vast majority of people living with HIV,
suspension is not recommended
because immediately there is a rebound, the viral load rises, the viruses replicate, this impacts the immune system, the defenses go down and there may be clinical complications," he emphasizes. Cassetti.
In addition, the vast majority of people under treatment maintain their viral load undetectable, which also makes the virus untransmittable.
"Later we learned that patients who discontinue the medication over time can react worse. It is not something advisable to do," Urueña insists. "But at that time we did it and
surprisingly she did not have a rebound in viral load
."
The virus, which had caused the woman advanced disease and for which she had no longer received treatment for years, was practically inhalable: antibody tests were negative and no DNA for the virus was found.
"He looked like a person who had never had HIV," they
say.
Analía Urueña has followed the patient since 2005.
Thoroughly
Noting the exceptionality of the case, the doctors decided to study it in depth.
They resorted to the Virology laboratory of the Garrahan Hospital and worked together with Dr. Andrea Mangano.
Thus, they ruled out that women had characteristics of "elite controllers", who naturally control the infection without the need for treatment (it is estimated that they represent between 0.5 and 1.5% of the population with HIV).
In 2014,
Urueña presented the case at an international congress
.
Among the attendees, she was heard by Clifford Lane, Associate Director of Clinical Research and Special Projects at the National Institute of Allergy and Infectious Diseases (NIAD), which is a member of the United States National Institutes of Health (NIH), who He suggested that they carry out more complex studies there.
The patient traveled with her two doctors on two occasions, in 2015 and 2017, to the NIH headquarters in Bethesda, Washington.
After signing the informed consent, he underwent biopsies of lymph nodes,
30 of the intestine
, leukapheresis (more specific blood cell analysis) and lumbar puncture to obtain cerebrospinal fluid, in order to search for virus reservoirs.
The studies, carried out in different specialized laboratories in the United States, found traces or fragments of virus in the brain biopsy, in the lymph node and T cell response to HIV antigens.
This documents that
the patient was infected
, even though the test is negative.
To confirm that the HIV diagnosis made in 1996 was not a false positive, the doctors were also able to rescue a sample of brain tissue stored at the Naval Hospital, which they confirmed was infected at that time.
"This is the
first report of complete seroreversion
(N of R: ie loss of antibodies), prolonged virus suppression after treatment, a profoundly small HIV reservoir, and persistent HIV-specific T cells in an adult with previous AIDS." , conclude the Argentine doctors, along with Clifford Lane and other NIH researchers in an article recently published in the
Open Forum Infectious Diseases
.
The last measurement with undetectable viral load was reported in February 2020.
"
It's a unique case among aftercare controllers
," says Cassetti.
Post-treatment controllers are a special population of people living with HIV who maintain undetectable viral load without treatment for a long time.
The largest series described so far is the Visconti cohort, which includes 27 cases.
"Each post-treatment controller is unique. This case from Buenos Aires is interesting due to the
very complete clinical, immunological and virological evaluation,
" Asier Saez-Cirion, principal investigator of the VISCONTI study, said in dialogue with aidsmap.com. the Argentine patient.
The characteristics that configure the "Patient from Buenos Aires" as an exceptional case is that she is a person with advanced disease with sustained virological remission without antiretroviral medication for 12 years,
one of the longest examples of post-treatment control
, in addition to the loss of antibodies, a very unusual phenomenon.
"It is thought that by having a small amount of virus, they do not act as antigens to generate them," explains Cassetti.
Cassetti is currently one of the researchers in the local study of a preventive vaccine against HIV.
Photo Lucia Merle.
Berlin-London-Buenos Aires
Is it similar to the cases of the Berlin and London patients?
No. Timothy Ray Brown - who died in September from leukemia - and Adam Castillejo were cured of HIV after receiving bone marrow transplants to treat oncohematological diseases they suffered.
In both cases, donors with the CCR5 mutation, which provides natural immunity against the virus, were sought.
In the case of Argentina,
there was no directed intervention
.
And Brown had even kept the antibodies.
In this case, there is no talk of a real cure, which implies that there is no virus in peripheral blood or in any reservoir.
Some authors speak of a functional cure, a concept that the researchers prefer to avoid and instead speak of
sustained virological remission
.
"Although it
is not clear how this patient managed to control the virus
, this case opens the door for future research that will lead us to find the mechanisms to control the virus and design strategies that lead to a definitive cure for HIV," they say. .
"The article is very interesting. It is one of the few cases in which one can speak of post-treatment control, in this case prolonged. And it has the particularity of being a patient who has a medical history that indicates that she met the criteria for a disease advanced ", affirms in dialogue with
Clarín
the infectologist Pedro Cahn, scientific director of the Fundación Hupedes and Argentine reference in research in HIV-AIDS, who did not participate in the investigation.
"I think this has to be looked at in two ways," adds Cahn, "
not to generate expectations
in the general population living with HIV that could lead one to think that the cure is just around the corner; but at the same time it is very stimulating to see that there are cases in which the post-treatment remission situation occurs. This indicates that we are on the right track to continue looking for alternatives to obtain a cure. It is a positive sign, we must congratulate the authors for their work, which is very well done and documented, but at the same time warning the community that it is a case that opens the way for more studies,
not for practical effects in the practice today
. "
Urueña highlights an article entitled
Learning from exceptions
.
"And this is an exception. A very rare, unique case. The idea of studying these people is to try to
find something in common,
" he says.
"This serves to tell the scientific community 'there are patients who may be different' and that it is worth delving into that. But without losing focus of our present time: we have to
test and treat more people, advance in pre-exposure prophylaxis ( PrEP)
, as the epidemic continues to grow. "