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HIV: 20 months' remission after a bone marrow transplant with no protective mutation – the Geneva patient

20 juli 2023

https://www.iasociety.org/news-release/ias-2023-highlights-advances-in-hiv-prevention-treatment-and-cure-research

In February 2023, the IciStem consortium, which includes Asier Sáez-Cirión's team at the Institut Pasteur, published details in Nature Medicine of a third case of HIV remission after a bone marrow transplant, involving the Düsseldorf patient. A total of 5 individuals (the Berlin, London, Düsseldorf, New York and City of Hope patients) are now considered as having probably been cured of HIV infection after receiving a bone marrow transplant. In all these cases, the bone marrow was taken from donors carrying the rare genetic mutation CCR5-delta 32, which is known to provide cells with natural protection against HIV. At the International Conference on HIV Science (IAS 2023), Asier Sáez-Cirión, Head of the Institut Pasteur's Viral Reservoirs and Immune Control Unit, and Professor Alexandra Calmy, MD, PhD and HIV/AIDS Unit Director at the Geneva University Hospitals (HUG), will present a case of HIV remission following a bone marrow transplant performed as part of the patient's cancer treatment. The significance of this patient monitored in Geneva at the HUG, whose case is being examined jointly by the Institut Pasteur, Institut Cochin and the IciStem consortium, lies in the fact that the transplant was taken from a donor who does not carry the CCR5-delta 32 mutation. Therefore, unlike the cells of other individuals who are considered to have been cured, this person's cells remain HIV-permissive. Despite this, the virus was still undetectable 20 months after antiretroviral therapy was discontinued. These findings will be presented orally in Brisbane, Australia on July 24, 2023.

The individual, whose circumstances will be outlined in the presentation, has been living with HIV since the early 1990s and received antiretroviral therapy from the outset. In 2018, he underwent a stem cell transplant as treatment for a particularly aggressive form of leukemia. One month after the transplant, tests showed that the patient's blood cells had been entirely replaced by the donor's cells, and this was accompanied by a significant reduction in the number of HIV-infected cells. Antiretroviral therapy was gradually reduced and permanently discontinued in November 2021.

Tests performed over the 20 months following therapy discontinuation found no viral particles, no latent viral reservoirs or any increase in the immune response against the virus in the individual's body. Although this evidence does not rule out the persistence of the virus in his body, the scientific team can nevertheless classify the "Geneva patient" as a case of remission from HIV infection.

"What has happened to me is wonderful and magical – we can now focus on the future," the Geneva patient.

"Although this protocol is not applicable on a large scale due to its aggressiveness, this new case provides unexpected insights on mechanisms of eliminating and controlling viral reservoirs, which will play a key role in devising curative HIV treatments," Asier Sáez-Cirión, Head of the Institut Pasteur's Viral Reservoirs and Immune Control Unit.

"Through this unique situation, we are exploring new avenues in the hope that HIV remission or even cure will one day no longer be a one-off occurrence," Alexandra Calmy, HIV/AIDS Unit Director at the Geneva University Hospitals.

Source
Absence of viral rebound for 20 months without antiretrovirals after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells to treat a biphenotypic sarcoma, oral presentation, IAS 2023, July 2023 
Asier Sáez-Cirión1, Anne-Claire Mamez2, Véronique Avettand-Fenoel3, Paul Thoueille4, Mitja Nabergoj5, Maxime Hentzien6, Ellen Mereles Costa6, Maria Salgado7, Monique Nijhuis8, Adeline Melard3, Elise Gardiennet3, Valérie Monceaux1, Caroline Passaes1, Anais Chapel1, Federico Perdomo-Celis1, Annemarie Wensing8, Javier Martínez Picado7, Sabine Yerly9, Mathieu Rougemont10, Alexandra Calmy6; and ICISTEM study group 

1 Institut Pasteur, Université Paris Cité, Viral reservoirs and immune control unit, Paris, France
2 Geneva University Hospitals, University of Geneva, Division of Hematology, Department of Oncology, Geneva, Switzerland 
3 Institut Cochin - CNRS 8104 / INSERM U1016 / Université de Paris, Paris, France 
4 Lausanne University Hospital and University of Lausanne, Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne, Switzerland 
5 Institut Central des Hôpitaux, Sion, Switzerland 
6 HIV/AIDS Unit, Infectious Diseases Department, Geneva University Hospitals, Geneva, Switzerland 
7 AIDS Research Institute, IrsiCaixa, Badalona, Barcelona, Spain 
8 University Medical Center Utrecht, Utrecht, Netherlands, 
9 Geneva University Hospitals, Laboratory of Virology, Geneva, Switzerland 
10 Private practitioner, Geneva, Switzerland

Contact
Institut Pasteur Press Office
MYRIAM REBEYROTTE +33 (0)1 45 68 81 01
ANNE BURLET-PARENDEL +33 (0)1 86 46 79 32
presse@pasteur.fr
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In memoriam Timothy Brown

30 september 2020
With great sadness we have been informed that Timothy Brown, known as the “Berlin Patient”, has passed away on Tuesday September 29th at 3.00 hours PM PST, due to leukemia.

Stem cell transplantation
 Timothy was diagnosed with HIV in 1995. In 2007 he was diagnosed with leukemia when he was living and working in Berlin as a translator. During his stem cell treatments for leukemia, doctors discovered that not only had the leukemia gone into remission, but Timothy’s HIV had been cured. No signs of HIV had been found since.

Earlier this year, the leukemia resurfaced and had spread widely through his body. The past few weeks Timothy received home hospice care in his apartment in Palm Springs, California. His partner, Tim Hoeffgen, has never left his side.

Source of inspiration
Timothy has been and is still a great inspiration for HIV/AIDS patients and scientists for all over the world. He was an active public figure in the HIV/AIDS arena and embodies a shared hope for a practical cure.

Timothy was also the source of inspiration for the IciStem study and was actively involved in the project as member of the community board.

Timothy was very enthusiastic about the two other IciStem patients that have not experienced HIV rebound after treatment interruption. He felt his family of cured persons was extended. Before he deceased Timothy expressed the importance of a cure for all and asked scientists and donors to keep fighting for a cure that works for everyone. He will be genuinely missed.

Our thoughts are with Tim, his family members and loved ones.

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Study supports claim HIV cure

12 maart 2020

Study supports claim of HIV cure in a second patient. No rebound of HIV in the London Patient who has stopped antiretroviral therapy after a successful stem cell transplantation to treat his hematological disease.

The so-called London Patient (IciStem patient #36) underwent a stem cell transplantation as part of his cancer treatment. The transplanted donor cells had a gene defect (CCR5delta32mutant), which renders these donor cells resistant against most HIV variants. Now, our study shows that 30 months after stopping antiretroviral therapy, no viral rebound has been observed in the London Patient.

This is the longest HIV remission after stem cell transplantation since the Berlin patient, who was the first person cured of HIV. Although traces of HIV were found in the Berlin Patient, HIV never rebounded and he is now celebrating his 13th  anniversary of being cured. The transplanted cells from a CCR5delta32 donor most likely protected his immune system. He also received aggressive chemotherapy, total body irradiation and two stem cell transplants. For over a decade, the HIV field has been puzzled regarding which of these factors were essential for his cure.

Professor Ravi Gupta of the University College London and the University of Cambridge, published a late-breaker abstract at CROI and an article on the London Patient in The Lancet HIV. In absence of a viral rebound 30 months after treatment interruption, several blood, semen, cerebrospinal fluid and tissue samples, including gut, lymph node and rectal tissue, were assessed. Using an arsenal of ultrasensitive techniques low levels of HIV DNA could be detected in lymph node tissue and blood cells, whereas HIV was undetectable in all other samples. Importantly, we demonstrated that the low levels of DNA that could be detected did not represent intact replication competent virus. The HIV DNA traces were also found in the first patient to be cured, the Berlin Patient. Scientists suggest that these remains can be considered as “fossils”, since they are incapable of reproducing the virus.

Dr. Björn Jensen of the Heinrich Heine University in Dusseldorf presented another HIV-infected patient (IciStem patient #19) who received a stem cell transplantation with these special donor cells (CCR5delta32mutant). The Dusseldorf patient interrupted his antiretroviral therapy 14 months ago and no viral rebound has been detected ever since. At CROI, it was demonstrated that no HIV DNA could be detected in blood T-cell subsets and gut biopsies (duodenum, ileum and rectum). In lymph node and gastrointestinal tract tissues traces of HIV DNA were shown using DNA scope. Since all functional assays were negative, it is likely that these traces do not represent replication competent virus. These results are compatible with sustained remission of HIV.


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New York Times: H.I.V. Is Reported Cured in a Second Patient, a Milestone in the Global AIDS Epidemic

10 mei 2019

Scientists have long tried to duplicate the procedure that led to the first long-term remission 12 years ago. With the so-called London patient, they seem to have succeeded.

For just the second time since the global epidemic began, a patient appears to have been cured of infection with H.I.V., the virus that causes AIDS.

The news comes nearly 12 years to the day after the first patient known to be cured, a feat that researchers have long tried, and failed, to duplicate. The surprise success now confirms that a cure for H.I.V. infection is possible, if difficult, researchers said. Please read the full article here.

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Information for patients - CROI 2019

4 maart 2019

IciStem investigates systematically the HIV reservoir in people living with  HIV who either had or may get an allogeneic stem cell transplantation. Each patient registered at the IciStem program participates in a local study led by his/her treating physicians. IciStem advises systematic collection of clinical data and blood, tissue and CSF samples before and after the stem cell transplantation. The IciStem consortium contains a network of highly specialized expert laboratories that can perform the most sensitive tests available to date to measure the HIV reservoir and the quality of the immune system.

Despite all the sensitive tests available to date, the only way to evaluate whether the HIV reservoir has been controlled or cleared is to interrupt antiretroviral therapy (ART).  However, ART interruption must only be performed by patients who have been informed about the risk of therapy interruption and have   signed an informed consent. Furthermore, interruption of ART should be performed in a controlled clinical setting with monitoring over time of a possible viral rebound and the ability for scientifically evaluation.

IciStem is very grateful for all participating patients for assisting in the search for a cure. We understand that the news about patients who discontinued therapy and did not experience a viral a rebound thus far is hope giving. We want to emphasize this has been done after thoroughly testing of the HIV reservoir and with strict monitoring

People living with HIV who have received or will receive an allogeneic transplantation and who are interested to be registered to IciStem, may ask their treating physician to contact the IciStem team.

We can imagine that the HIV positive patients who do not have a hematological disease requiring a stem cell transplantation  visiting our website, would like to participate. Unfortunately, stem cell transplantation is an high risk procedure which comes with a high mortality and patients who do not have a hematological disease requiring a transplantation can therefore not be registered. We do hope we can provide knowledge in the nearby future which can translate the results of IciStem to a broader group of people living with HIV.


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Press release "A step closer to HIV cure" - CROI 2019

4 maart 2019
A step closer to an HIV cure. No rebound of HIV in two patients who stopped taking their HIV medication after stem cell transplantation for a hematological disease

Medical experts have found no evidence of an infectious virus for months in two HIV patients who stopped their antiviral medication. Both patients underwent stem cell transplantation as part of their cancer treatment. The transplanted donor cells had a gene defect (CCR5delta32mutant), which results in the absence of one of the critical entry gatekeepers that HIV generally needs to infect cells. One of the patients has been without antiretroviral treatment for 18 months, so experts are especially optimistic regarding a possible cure. The other case of HIV was undetectable after 3,5 months without antiviral medication.

Thus far, only one person in the world, ‘the Berlin patient’, has been cured of HIV. Although traces of HIV were found, HIV never rebounded and he is now celebrating his 12th anniversary of being cured. The transplanted cells from a CCR5delta32 donor most likely protected his immune system. He also received aggressive chemotherapy, total body irradiation and two stem cell transplants. For over a decade, the HIV field has been puzzled regarding which of these factors were essential for his cure.

Today, Professor Ravi Gupta of the University College London and the University of Cambridge, presented the breaking news of a new case with a possible HIV cure at the international Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle and will be published in Nature today. His London patient has not experienced HIV rebound during the 18 months after he stopped taking his antiviral medication. This is the longest adult HIV remission after stem cell transplantation since the Berlin patient. Usually, when HIV+ individuals stop treatment, the virus rebounds within the first month.

A second potential cure from HIV after stem cell transplantation will be presented by Dr. Björn Jensen from Düsseldorf University. This patient stopped using his HIV medication for a shorter period of 3,5 months and has also remained HIV free. In previous cases of antiretroviral interruption after a stem cell transplant without the CCR5 Delta 32 mutation, the virus rebounded at month 3, 8 and 10, respectively.

The patients were investigated by internationally renowned researchers. Both patients are registered to the IciStem program.  IciStem is a joint venture of collaborating researchers and clinicians who share their expertise on HIV cure and stem cell transplantation to gain insight into the mechanisms of HIV eradication.  

In both patients only traces of HIV DNA were detected with the most sensitive techniques available to date, similar to the case of ‘the Berlin patient’. According to the principal investigators of IciStem, P. Annemarie Wensing, from the University Medical Center of Utrecht (The Netherlands),  and Javier Martinez-Picado, from the IrsiCaixa AIDS Research Institute (Barcelona, Spain), these cases support the further investigation of CCR5 related gene therapy.

The cases show that, even with one transplant, mild cancer chemotherapy and without radiation, remission may be achieved.

Today, 39 patients who are registered with the IciStem program have received a transplant. IciStem has the largest program to investigate HIV cure following stem cell transplantation, and has identified more than 22,000 donors with the rare CCR5delta32 gene defect. IciStem investigator Gero Hütter, who was the physician who performed the transplant on the ‘Berlin patient’. was instrumental in this aspect  of the program .  IciStem is funded by the Foundation for AIDS Research (amfAR).


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Work from the IciStem consortium has been rewarded at the EBMT!

26 maart 2018

During the Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Jon Badiola has been awarded with one of the Best Young Abstract Awards. Jon Badiola is a Hematology resident at the Virgen de Las Nieves University Hospital in Granada, Spain. His work is united in the IciStem Consortium and Jon was an author of the abstract that has been awarded: "HIV status in long-term follow-up after allogeneic stem cell transplantation: the “Granada patients”". The abstract was selected from the top-scored abstracts submitted by young physicians. This is a wonderful achievement, thank you all for making this possible!

Jon Badiola
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The IciStem project is supported by AmfAR Research Consortium on HIV eradication (ARCHE) Research Grant # 109858-64-RSRL and the Aidsfonds


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