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  International AIDS Conference
Durban, South Africa
July 18-22 2016
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Allogeneic Stem Cell Transplantation in HIV-1 infected individuals; the EpiStem Consortium
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Reported by Jules Levin
IAS Durban HIV cure Symposium July 16-17 2016
Information on the project
EpiStem 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 EpiStem consortium consists of hematologists with extensive experience in allogeneic SCT procedures in HIV-infected patients, along with infectious disease specialists, virologists and immunologists with expertise in the field of HIV-1 tropism, innate and adaptive immunity, pharmacology, reservoirs and cure. EpiStem has built an inventory in European blood banks of CCR5Δ32/32 or heterozygous (cord)blood donors. The experts are available for guidance in donor search and CCR5 screening, ethical regulations, the SCT procedure, sampling procedures and in depth investigations to study HIV persistence. Clinicians of HIV infected patients who require an SCT may register their patient in the EpiStem observational cohort. We collect clinical information and virological and immunological characteristics of a variety of samples taken before and after SCT according to an advanced monitoring and sampling strategy.
EpiStem aims to better understand the implications of stem cell transplantation in the control and eradication of HIV.
Long term goals
We analyze over time the viral reservoirs and the immune reconstitution within the patients included in EpiStem. The knowledge as gathered in EpiStem will provide in-depth insight in the viral reservoirs and biological determinants of cure essential for HIV eradication strategies.


European Project to guide and investigate the potential for HIV cure by Stem Cell Transplantation (EpiStem)
EpiStem is an observational project, which studies HIV infected patients who receive stem cells from another person (Allogeneic Stem Cell Transplantation). The patients all undergo this procedure because of life-threatening hematological conditions. The project aims to improve the interventions to cure these patients with the additional aim to better understand the biological mechanisms leading to reduction of viral reservoirs in the body and to identify potential cases of HIV-1 eradication/remission. EpiStem is not a clinical trial, but systematically monitors the patients before and for extensive periods of time after the stem cell transplantation.
The EpiStem investigators form a European Consortium of hematologists, infectious disease specialists, virologists, immunologists and blood/tissue bank specialists from France, Germany, Spain, the Netherlands and the United Kingdom who collaborate with clinicians globally to enroll patients to study blood and tissue samples before and after the stem cell transplantation. The project is co-led by Javier Martinez-Picado, ICREA researcher from the IrsiCaixa AIDS Research Institute (Barcelona, Spain), and Annemarie Wensing, clinical virologist from the University Medical Center Utrecht (Netherlands). Funding comes from amfAR Research Consortium on HIV Eradication (ARCHE), a program from the US Foundation for AIDS Research, amfAR.
Twenty-four individuals are being studied. Of these, 15 patients have received stem cell transplantation. A subset of these patients have received stem cells from donors who, due to a genetic variation, do not display a protein called CCR5 receptor on their cells. This protein is commonly used by HIV to enter human cells.
This kind of donor cells was also used for the stem cell transplantation of the Berlin patient, the only person to date who has been cured from HIV-infection. As part of EpiStem cord blood units and bone marrow adult donors are continuously being characterized across Europe to increase availability of donor cells lacking the CCR5 receptor.
Initial data from the EpiStem consortium show that Allogeneic Stem Cell Transplantation systematically reduces HIV-1 reservoirs independent of the procedure and type of donor used.
In three patients who are in follow-up after stem cell transplantation for more than one year, we have performed the most sensitive analyses available to date. In two of these patients we cannot detect HIV in the blood. Like in the Berlin patient we were also able to test tissue and we could only find a trace of HIV in tissues of these patients. All patients in EpiStem are still on antiretroviral therapy; therefore, we do not know whether they are cured from HIV-infection. One could only confirm cure if therapy was discontinued and no viral rebound occurred.
Currently Stem-cell transplantation is not an option that can be widely applied, since it is a high-risk procedure. However, Annemarie Wensing explained today in Durban at the international AIDS conference that studying patients who require the procedure for other conditions could provide important new insights for eradication of HIV, which currently infects about 37 million people worldwide. EpiStem aims to prospectively continue recruiting new cases of allogeneic SCT in HIV-1-infected individuals. Information on the project can be received through EpiStem@umcutrecht.nl or a.m.j.wensing@umcutrecht.nl or at www.epistem-project.org