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HIVACAT

IrsiCaixa leads the first umbilical cord stem cells transplantation resistant to HIV infection in a patient with severe blood disease

20/05/2015

  • ‘Lancet HIV’ journal publishes the case “Barcelona Patient”, who suffered from lymphoma and had an umbilical cord stem cells transplantation with a HIV-resistant mutation. The transplantation regenerated his immune system cells and made them resistant to HIV. Although the patient died three months later due to cancer progression, HIV was no longer detectable in his cells. 
  • Other 11 haematological HIV-patients from Europe have had or will soon have a stem cell transplantation. Interventions are performed under the Epistem international consortium, led by the IrsiCaixa AIDS Research Institute, promoted by the Obra Social "la Caixa" and the Health Department of the Generalitat de Catalunya, and the University of Utrecht. Haematologist who first performed this type of transplantation, in 2009, and experts from the Gregorio Marañón Hospital in Madrid are also collaborating. The project is funded by amfAR.
  • IrsiCaixa has worked with haematologists of the Institut Català d’Oncologia (ICO) and scientists of the Banc de Sang i Teixits (BST). 
  • The stem cell transplantation is a high-risk procedure, only recommended in patients with severe blood disease. Nonetheless, studying this process will reveal the mechanism that stops the spread of the virus and will offer clues to reproduce it in other patients, without a transplantation.

CCR5-Delta32 mutation is a rare blood disorder that affects approximately 1% of the European population. It is known that people who have this gene mutation are naturally resistant to HIV, because it prevents the virus from entering its target cells, CD4 T lymphocytes. In 2009, Timothy Brown, known as the "Berlin patient", became the first HIV-cured person in the world after having a bone marrow stem cells transplantation with this mutation. Today, May 20th, 2015, Spanish researchers led by the IrsiCaixa AIDS Research Institute, promoted by the Obra Social "la Caixa" and the Health Department of the Generalitat de Catalunya, publish in Lancet HIV journal the case of another patient, this time from Barcelona, who had an umbilical cord stem cells transplantation with this mutation in 2013. In IrsiCaixa, the project was coordinated by ICREA researcher Javier Martinez-Picado and researcher Maria Salgado.

“Barcelona patient”, a 37-years old man, suffered from an aggressive lymphoma and was HIV-infected. Hematologists from the Institut Català d’Oncologia, in collaboration with IrsiCaixa researchers and Banc de Sang I Teixits scientists, performed a stem cells transplantation with the CCR5-Delta32 mutation. Stem cells came from umbilical cord instead of bone marrow, so the possibilities of finding a compatible donor carrying the mutation were multiplied by 100.

Transplant regenerated immune system cells, making them resistant to HIV. After surgery, his blood was tested weekly and it was found that viral reservoirs (virus that remain dormant inside cells and react when antiretroviral treatment is interrupted) had fallen to undetectable levels. Furthermore, it was observed in cells removed from the patient that they were not infected when exposed to HIV in the laboratory. Lymphoma, however, progressed and the man died 3 months later, so researchers did not have time to stop treatment and check whether the virus was completely eradicated from his body.

Stem cells transplantation is a high-risk procedure, only recommended in severe blood cancer, so this it is not a cure strategy that could be generalized.

 

Other cases in Europe

Besides the “Barcelona Patient”, the scientific team currently has 11 other HIV-positive candidates for stem cell transplant: 6 in Spain, 2 in the Netherlands, 2 in Germany and 1 in Belgium. Eight transplants have already been done and 3 (2 in Madrid and 1 in Ghent) will be done in the coming months. The final results are still being evaluated. Not all the transplantations had the CCR5-Delta32 mutation, since donors carrying the mutation haven’t always been found to each patient. IrsiCaixa is currently investigating how to artificially modify stem cells from each patient to induce a mutation that could make them resistant to HIV infection and allow to make an autologous transplantation, which would increase the possibilities of success of interventions.

Interventions are made in the context of EpiStem international consortium, led by IrsiCaixa AIDS Research Institute and the University Medical Center Utrecht. Experts from the Gregorio Marañón Hospital in Madrid also collaborate in the project. EpiStem, co-led by ICREA IrsiCaixa researcher Javier Martinez-Picado, is funded by amfAR Research Consortium on HIV Eradication (ARCHE), a program of the US Foundation for AIDS Research, amfAR.

EpiStem aims to better understanding which mechanism can stop the spread of the virus in patients who need a transplantation because of their hematological condition, in order to improve the interventions and try to cure all HIV-infected people. The genetic mutation seems to be the main factor that determines success, but there are other steps in the clinical process that could also contribute.

The team is still recruiting HIV-patients who need a blood transplant. Contacts to join the project can be approached through epistem@irsicaixa.es.