WEPEA065
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Title
Allogeneic stem cell transplant in HIV-1 infected individuals; An update of the IciStem Consortium
Presenter
Annemarie M.J. Wensing
Authors
A.M.J. Wensing1, M. Salgado2, M. Kwon3, J.M. Eberhard4, A. Saez-Cirion5, J. Schulze zur Wiesch4, G. Hütter6, J. Badiola-González7, A. Bandera8, L. Barrett9, R.K. Gupta10, B.E. Jensen11, J.H.E. Kuball12, L. Martín Carbonero13, M. Nabergoj14, K. Raj15, R. Saldaña-Moreno16, G. Scarlatti17, L. Vandekerckhove18, J.L. Díez Martín3, M. Nijhuis19, J. Martínez-Picado2, IciStem Consortium
Institutions
1University Medical Center Utrecht, Translational Virology, Department of Medical Microbiology, Utrecht, Netherlands, 2IrsiCaixa AIDS Research Institute, Barcelona, Spain, 3Gregorio Marañón Hospital, Madrid, Spain, 4University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 5Institut Pasteur, Paris, France, 6Cellex Gesellschaft für Zellgewinnung mbH, Dresden, Germany, 7Virgen de Las Nieves University Hospital, Granada, Spain, 8ASST Monza - San Gerardo Hospital, Monza, Italy, 9Dalhousie University Halifax, Halifax, Canada, 10University College London Hospitals NHS Foundation Trust, London, United Kingdom, 11Düsseldorf University Hospital, Düsseldorf, Germany, 12University Medical Center Utrecht, Cancer Center, Utrecht, Netherlands, 13Hospital La Paz, Madrid, Spain, 14Geneva University Hospital, Geneva, Switzerland, 15King's College Hospital NHS Foundation Trust, London, United Kingdom, 16Hospital General de Jerez de la Frontera, Jerez de la Frontera, Spain, 17San Raffaele Hospital, Milan, Italy, 18Universitair Ziekenhuis Gent, Ghent, Belgium, 19University Medical Center Utrecht, Utrecht, Netherlands

Background: Allogeneic Stem Cell Transplantation (SCT) in HIV infected individuals has the potential to cure HIV as has been observed in the Berlin patient. Although this high-risk procedure is only indicated for certain hematological malignancies, the strategy raised tremendous scientific potential to gain profound insight in the mechanisms of HIV eradication.
Methods: The IciStem consortium aims to guide clinicians of HIV-infected patients who require an SCT in donor search and CCR5 screening, ethical regulations, the SCT procedure, sampling procedures and in depth investigations to study HIV persistence. The patients are registered to the IciStem observational cohort. Viral tropism, the remaining HIV reservoir and cellular and humoral immunity are investigated thoroughly.
Results: As part of IciStem efforts, 32,000 cord blood units and 2,200,000 bone marrow adult donors have been genotyped for CCR5 in multiple blood banks around Europe to increase CCR5Δ32 donor availability. 44 HIV-positive patients with diverse hematological malignancies have been registered to the IciStem cohort. 38 patients have been transplanted with CCR5Δ32 (n=9), heterozygous (n=3) or CCR5 WT donors. So far, 19 patients have successfully passed the 12 months follow-up after transplantation, and 13 patients have died after transplantation, despite achieving full donor chimerism in most cases. Preliminary analysis of virological and immunological data from blood and tissue samples shows a systematic reduction of HIV-1 reservoirs and a diminishing humoral immunity with (partial) seroreversion. Out of the 4 patients with a CCR5Δ32 homozygous donor that are still on follow up, two patients have interrupted antiviral therapy and did not rebound during the observation time. Five CCR5WT participants with proven undetectable viral reservoirs are in the process of initiating a combination of an immune therapy (bNAbs: 10-1074+3BNC117) with ATI.
Conclusions: IciStem is the largest registry studying in depth the HIV reservoir and the respective immune system after allo-HSCT. A potential eradication of the reservoir is currently evaluated by treatment interruption alone or in combination with bNAbs.