International Collaboration to guide and investigate the potential for HIV cure by Stem Cell Transplantation

IciStem is a collaborative project to guide and investigate the potential for HIV cure in HIV-infected patients requiring allogeneic stem cell transplantation for hematological disorders.

The IciStem consortium is composed of an expert European review panel of hematologists with experience in allogeneic SCT procedures along with infectious disease specialists, virologist and immunologists with expertise in the field of HIV-1 tropism, reservoirs and cure.

We prospectively study allogeneic SCT recipients with HIV-1 infection, collecting complete information on underlying malignancy, chemotherapy, transplant procedure, donor selection, HIV-tropism, cART, and virological and immunological characteristics of a variety of samples before and after the transplant.

Information for patients

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. Read more here.

Consortium statement on treatment interruption

Successful treatment of HIV is the suppression of the virus in the blood as measured through blood tests. While the virus is suppressed in the blood - registering undetectable in blood tests - the virus remains in infected cells in a dormant state (the ‘viral reservoir’). When treatment is interrupted the virus usually rebounds in the blood to detectable levels within 2–3 weeks from the release of infectious virus from the viral reservoir.

Treatment of HIV-patients has improved drastically over the past years, new developments are on the rise, and an HIV cure is gradually becoming a more realistic outcome. The only way to evaluate the effectiveness of a functional (virological control in the absence of antiretroviral therapy) or sterilizing (virus eradication) cure of HIV is to interrupt antiretroviral therapy (ART).

ART interruption must only be performed in a controlled clinical setting with monitoring over time of the viral rebound and the ability for scientifically evaluation.

Towards finding new strategies and a cure for HIV IciStem encourages and supports treatment interruption in a clinical setting with the consent of an HIV+ individual. IciStem strongly discourages treatment interruption in any uncontrolled setting.

In choosing to participate in HIV scientific research HIV+ individuals should understand the risks of a viral rebound from their viral reservoir, which may lead to acute retroviral syndrome, increased risk of HIV transmission, accelerated disease progression, and the possible development of drug resistance.

The IciStem consortium respects and appreciates the risks HIV+ individuals are willing to take in helping us scientifically pursue cure research. IciStem consortium members strongly advise patients who are willing to interrupt/stop their treatment to discuss this with their clinician prior to interruption, and to only do it under medical/clinical supervision. If you do this in the IciStem consortium we will provide advice on when and how to proceed based on our evaluation of cure research protocol and actively partner with you towards minimizing the risks to you during treatment interruption.

NEWS

Press releases

Cure of IciStem participant #19 The Düsseldorf patient.
A 53-year-old man in Germany has become at least the third person with HIV to be declared cleared of the virus after a procedure that replaced his bone marrow cells with HIV-resistant stem cells from a donor. Read more about this in Nature magazine and the dutch newspaper Trouw.

Webinar for the HIV community
After the CROI conference we will organize a webinar for the HIV community with recent findings from IciStem, if you would like to receive the announcement please sent us your email.

In memoriam

Timothy Brown

With great sadness we have been informed that Timothy Brown, known as the “Berlin Patient”, has passed away on Tuesday September 29th, due to leukemia. He has been and is still a great inspiration for HIV/AIDS patients and scientists for all over the world. Timothy was also the source of inspiration for the IciStem study. Read the full message here.

Recent publications and presentations

In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation
Björn-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Lübke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Gálvez, Christiane Mummert, Caroline Passaes, Johanna M. Eberhard, Carsten Münk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gábor A. Dunay, Florian Klein, Dieter Häussinger, Johannes C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Sáez-Cirión, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado & Guido Kobbe

Nature Medicine (2023) Feb 20

Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells.

Huyveneers LEP, Bruns A, Stam A, Ellerbroek P, de Jong D, Nagy NA, Gumbs SBH, Tesselaar K, Bosman K, Salgado M, Hütter G, Brosens LAA, Kwon M, Diez Martin J, van der Meer JTM, de Kort TM, Sáez-Cirión A, Schulze Zur Wiesch J, Boelens JJ, Martinez-Picado J, Kuball JHE, Wensing AMJ, Nijhuis M

IciStem Consortium.Viruses. 2022 Sep 17;14(9):2069. doi: 10.3390/v14092069.PMID: 36146874.

Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

Johanna M. Eberhard, Mathieu Angin, Caroline Passaes, Maria Salgado, Valerie Monceaux, Elena Knops, Guido Kobbe, Björn Jensen, Maximilian Christopeit, Nicolaus Kröger, Linos Vandekerckhove, Jon Badiola, Alessandra Bandera, Kavita Raj, Jan van Lunzen, Gero Hütter, Jürgen H. E. Kuball, Carolina Martinez-Laperche, Pascual Balsalobre, Mi Kwon, José L. Díez-Martín, Monique Nijhuis, Annemarie Wensing, Javier Martinez-Picado, Julian Schulze zur Wiesch and Asier Sáez-Cirión

Sci Transl Med. 2020 May 6;12(542):eaay9355. doi: 10.1126/scitranslmed.aay9355.

Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report

Ravindra Kumar Gupta, Dimitra Peppa, Alison L Hill, Cristina Gálvez, Maria Salgado, Matthew Pace, Laura E McCoy, Sarah A Griffith, John Thornhill, Aljawharah Alrubayyi, Laura E P Huyveneers, Eleni Nastouli, Paul Grant, Simon G Edwards, Andrew J Innes, John Frater, Monique Nijhuis, Annemarie J Wensing, Javier Martinez-Picado, Eduardo Olavarria

Lancet HIV. 2020 Mar 9. pii: S2352-3018(20)30069-2.

HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation.
Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes AJ, Muir L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E.

Nature. 2019 Apr;568(7751):244-248. doi: 10.1038/s41586-019-1027-4. Epub 2019 Mar 5.PMID: 30836379

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