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Confirmed the second case of HIV cure in the world

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The first was Timothy Brown known as «the Berlin patient » and now comes the so-called ‘London patient’. They are, for the moment, the only two people in the world who have been cured of HIV, the virus that causes AIDS. And they could join a third person, the «Patient from Düsseldorf», which has been without virus for 14 months in the absence of antiretroviral medication from a bone marrow transplant.

Magazine “The Lancet HIV” published Tuesday a study confirming the ‘cure’ of HIV of the so-called “London patient”, since 29 months after undergoing a stem cell transplant There is still no trace of virus replication in your body. The publication comes to light coinciding with the Conference of Retrovirus and Opportunistic Infections (CROI) to be held in Boston (USA) but that due to COVID-19 takes place virtual.

The lead author of the study, Professor Ravindra Kumar Gupta of the University of Cambridge (United Kingdom) underlines that «these results represent the second case of a patient cured of HIV. Our findings show that the success of stem cell transplantation as a cure for HIV, first reported nine years ago in the Berlin patient, can be replicated.

Both cases are integrated into the IciStem consortium, coordinated by the Institute of AIDS Research IrsiCaixa, jointly promoted by «la Caixa» and the Department of Health of the Generalitat de Catalunya, and the ” Utrecht University Medical Center (Netherlands)». In this same congress, IciStem also presents the case of «» Patient from Düsseldorf », although this time we talk about long-term remission of HIV.

The magazine “Nature” published an article in which it was shown that he had been with the undetectable virus in his blood for 18 months, which made him the second case of “long-term remission”

The researchers differentiate the concepts of “cure” and “long-term remission” based on the time elapsed without viral rebound since the discontinuation of antiretroviral medication. “When the London case was initially published, we insisted on not talking about a cure because, although 18 months invited a lot of optimism because we had not seen such a long interval since the” Berlin patient “, we wanted to be prudent and not generate false expectations », He points out Javier Martínez-Picado, investigator ICREA at IrsiCaixa and co-coordinator of IciStem. Now, with 29 months of remission, researchers go one step further.

The new case of HIV cure is a man with HIV since 2003 who was detected a Hodgkin lymphoma, a disease that forms malignant (cancer) cells in the lymphatic system. For this reason he underwent a cell transplant in 2016 mother who had a mutation, called CCR5 Delta 32, which makes it impossible for the virus to enter target cells of HIV, CD4 T lymphocytes.

This intervention, very aggressive because of its high level of mortality (they do not survive it among a 40 and a 50 percent of the patients operated on), however, opened the door to healing. For Gupta it is «important to keep in mind that this treatment curative is high risk, and is only used as a last resort for patients with HIV who also have life-threatening hematologic malignancies. Therefore, it is not a treatment offered to patients with HIV who are on antiretroviral treatment.

“It is important to keep in mind that this curative treatment is high risk, and is only used as a last resort for patients with HIV who also have life-threatening hematological malignancies.

After 16 months, antiretroviral treatment was interrupted and, in March 2019, the magazine Nature He published an article showing that he had been with the undetectable virus in his blood for 18 months, making him the second case of “long-term remission.”

Now, the new work confirms that, 29 months after treatment discontinuation, the virus remains undetectable in blood, brain-spinal fluid, intestinal tissue and semen. The analyzes detect very high levels low HIV genome in lymphoid tissues, but it is a defective genetic material that has no replicative capacity and therefore has no infectious capacity. «All this pushes us to conclude that this is a second case of cure because in the Berlin Patient they were also detected fossil remains of viral DNA and without infectious capacity ”, explains Martínez-Picado.

While most HIV patients can control the virus with current treatment options and have the possibility of living a long and healthy life, experimental research of this type follows patients who have undergone high curative treatments. risk and last resort, can provide information about a cure in the future.

The London Patient also has antibodies against HIV, although at a very low level and that has undergone a continuous reduction since the transplant. Their presence could indicate that the new cells of the immune system could have been exposed to the virus, but according to the researcher at IrsiCaixa Maria Salgado, which is part dand IciStem“It is common for the body to persist evidence of a past infection, antibodies may take years to disappear.”

Compared to the treatment used in the Berlin patient, the authors emphasize that “the London patient” represents a further step towards a less intensive treatment approach, showing that long-term remission of HIV can be achieved using pharmacological regimens of reduced intensity, with a stem cell transplant (instead of two) and without total body irradiation.

However, being only the second patient to undergo this experimental treatment successfully, the authors point out that you will need a continuous controlor, much less frequently, for the reappearance of the virus.

What do these results mean for future developments of curative therapies for HIV using the CCR5 gene? For one of the study’s co-authors, Dimitra Peppa, from the Oxford University (UK), “The London and Berlin patient are examples of the use of the CCR5 gene in curative therapies outside of gene editing. There are still many ethical and technical barriers, for example, gene editing, efficiency and solid safety data, which must be overcome before any approach. The use of the CCR5 gene editing can be considered as a scalable cure strategy for HIV ».

The lack of rebound in these cases is due to the donor cells being resistant to HIV, and as they replace the recipient cells after transplantation, the chances of infection for the virus decrease

Usually, when people with HIV infection interrupt treatment, the virus bounces over the first 4 weeks. The lack of rebound in these cases is because the donor cells are resistant to HIV, and as they go replacing receptor cells after transplantation, the chances of infection for the virus, which ends up disappearing, decrease.

Despite the success, Martínez-Picado warns that “there are still certain barriers to be demolished before the genetic edition of the CCR5 receptor can be used as a scalable cure strategy for the entire population.”

Third case in remission

As for the ‘Düsseldorf patient’, This is a 50-year-old man with HIV who in February 2013 received a stem cell transplant to treat acute myeloid leukemia. Donor cells also had the mutation. CCR5 Delta32. In November 2018, doctors interrupted antiretroviral medication and, 14 months later, it still has no viral rebound. The analyzes show traces of virus DNA in the lymph nodes and the gastrointestinal tract, although without infectious capacity. According to the researchers, these results “are compatible with a sustained remission of HIV”.

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