Treatment of HIV and acute myeloid leukemia by allogeneic CCR5-d32 - PowerPoint PPT Presentation

Treatment of HIV and acute myeloid leukemia by allogeneic CCR5-d32 blood stem cell transplantation Elena Knops Elena Knops, GfV 2016

Background - the Berlin patient – so far the only person presumed to be cured from HIV by hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor Elena Knops, GfV 2016

Background - the Berlin patient – so far the only person presumed to be cured from HIV by hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor - failed attempts to reproduce cure by HSCT - viral rebound or death due to underlying malignancy Elena Knops, GfV 2016

Background - the Berlin patient – so far the only person presumed to be cured from HIV by hematopoietic stem cell transplantation (HSCT) from a homozygous CCR5-d32 donor - failed attempts to reproduce cure by HSCT - viral rebound or death due to underlying malignancy - THE question about all of these attempts and the Berlin patient: How to be sure about the cure? Is there any virus in the patient? Elena Knops, GfV 2016

The whole story (drama in 4 acts) 46y old patient alive, well and undetectable for HIV (RNA/DNA) over 3 years after allogeneic CCR5-d32 HSCT Elena Knops, GfV 2016

The beginning (prologue) induction consolidation Elena Knops, GfV 2016

The beginning (prologue) induction consolidation Elena Knops, GfV 2016

The beginning (prologue) induction consolidation Elena Knops, GfV 2016

Chapter I female donor, 10 out of 10 HLA- matched CCR5-d32 .... .... one week before SCT Elena Knops, GfV 2016

Chapter I female donor, 10 out of 10 HLA- matched CCR5-d32 .... .... one week before SCT Elena Knops, GfV 2016

Chapter I female donor, 10 out of 10 HLA- matched CCR5-d32 .... .... one week before SCT Elena Knops, GfV 2016

Chapter I female donor, 10 out of 10 HLA- matched CCR5-d32 .... .... one week before SCT Elena Knops, GfV 2016

Chapter II .... Elena Knops, GfV 2016

Chapter II total of 8 courses of 5-azacytidine + 4 donor lymphocyte infusions .... Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV Tacrolimus + topical steroids 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV Tacrolimus + topical steroids 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV Tacrolimus + topical steroids 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter III + CMV, HHV8, HSV Tacrolimus + topical steroids 10 10 10 0 0 0 .... <LOD (884250) in rectal and ileum biopsy Elena Knops, GfV 2016

Chapter IV gp160 gp120 gp41 p68 p55 p34 p25 p18 pos. control neg. control 02/2013 before SCT 06/2014 02/2015 07/2015 12/2015 01/2016 Elena Knops, GfV 2016

Hide-outs of HIV HIV reservoirs cellular anatomical - follicular - GALT dendritic cells - lymph nodes - macrophages - Liquor/CNS/CSF - resting CD4+ - urogenital tract cells „Can HIV be cured?“ Mario Stevenson Scientific American 299, 78 - 83 (2008) Elena Knops, GfV 2016

The end? (epilogue) - Viral outgrowth assay (EPISTEM: Javier Martinez-Picado, Barcelona): PBMCs (in progress) and lymph node (planned) - V3 phenotypes of the minority of the predicted X4 variants (EPISTEM: Monique Nijhuis, Utrecht) - T-cell response assay (Thomas Harrer, Erlangen): PBMCs (in progress) - proviral DNA load from further PBMC samples, biopsies and lymph nodes (Institute of Virology, Cologne and Gabor Dunay, HPI, Hamburg) - proviral DNA load from PBMCs from the time points of the AML relapse (in progress) European project to guide and investigate the potential for HIV cure by stem cell transplantation. The EPISTEM project is supported by amfAR Research Consortium on HIV eradication (ARCHE) Research Grant # 108930-56-RGRL www.epistem-project.org Elena Knops, GfV 2016

The end? (epilogue) THE question: How to be sure about the cure? Stop ART? What else? Elena Knops, GfV 2016

Thanks to our group University of Düsseldorf Institute of Virology, University of Cologne Hepatology & Infectiology Rolf Kaiser Björn Jensen Veronica Di Cristanziano Falk Hüttig Maria Neumann-Fraune Dieter Häussinger Eugen Schülter Claudia Müller Virology Saleta Sierra-Aragon Nadine Lübke Eva Heger Simon Lennartz Haematology Hermann Töpker Guido Kobbe Max Damagnez Stephanie Inden Moleculare Medizin Sascha Hasheminasab Philipp Lang Herbert Pfister Junnat Hamdam Institute for Immunogenetics, Kaiserslautern Martin Däumer, Alex Thielen Heinrich Pette Institut HH Gabor Dunay, Johanna Eberhardt, Silke Kummer, Julian Schulze zur Wiesch Med 3, University of Erlangen Thomas Harrer MASTER–HIV/HEP (RKI, Resina) Norbert Bannert, Barbara Bartmeyer, Osama Hamouda, Klaus Jansen, Claudia Kücherer, Andrea Hauser, Robert Koch Institut (RKI), Berlin Dept. Gastroenterologie, Krankenhaus der Augustinerinnen, Cologne Mark Oette MPI of Informatics, Saarbrücken Thomas Lengauer, Nico Pfeifer, Alejandro Pironti, Prabhav Kalaghatgi Elena Knops, GfV 2016