In the image, María Salgado and Javier Martínez-Picado, authors of this study. / IrsiCaixa
Five people infected with HIV who received a stem cell transplant now have the virus undetectable in blood and tissues. In one of them, researchers cannot even detect antibodies in their blood. This finding could be useful for the design of new strategies to cure the infection.
The viral reservoir, made up of cells infected by the virus that remain dormant and cannot be detected or destroyed by the immune system, is the reason that currently the drugs do not cure HIV infection.
Now, a study published in the Annals of Internal Medicine points out certain factors associated with stem cell transplantation that could contribute to the elimination of this reservoir in the body.
This conclusion comes after five patients who received a stem cell transplant have an undetectable HIV reservoir and one of them does not even have antibodies against the virus in their blood.
These results could be used to design less invasive HIV cure strategies, since stem cell transplantation is recommended exclusively to treat serious hematological diseases.
The study was co-directed by experts from the Institute for AIDS Research IrsiCaixa (Barcelona), jointly promoted by the Obra Social “la Caixa” and the Health Department of the Generalitat de Catalunya, and the General University Hospital Gregorio Marañón (Madrid).
The study is based on the case of the Berlin patient, Timothy Brown, a person with HIV who in 2008 underwent a stem cell transplant to treat leukemia.
The donor had a mutation called CCR5 delta 32 that made their blood cells immune to HIV, since it prevents the virus from entering them. Brown stopped taking antiretroviral medication and today, 11 years later, the virus still does not appear in his blood. He is considered the only person in the world cured of HIV.
Since then, scientists are investigating possible mechanisms of HIV eradication associated with stem cell transplantation. To do this, the IciStem consortium has created a unique cohort in the world of infected people who underwent a transplant to cure a blood disease, with the ultimate goal of designing new healing strategies.
“Our hypothesis was that, in addition to the CCR5 delta 32 mutation, other mechanisms associated with transplantation influenced the eradication of Timothy Brown,” explains María Salgado, a researcher at IrsiCaixa and co-author of the article.
The study included six participants who had survived at least two years after receiving the transplant. All donors lacked the CCR5 delta 32 mutation in their cells.
“We selected these cases because we wanted to focus on the other causes that could help eliminate the virus,” says Mi Kwon, a hematologist at the Gregorio Marañón Hospital and co-author of the article.
Undetectable reservoir in blood and tissues
After the transplant, all the participants maintained the antiretroviral treatment and achieved the remission of their hematological disease after the withdrawal of the immunosuppressive drugs.
After several analyzes, the researchers saw that five of them had an undetectable reservoir in blood and tissues. This fact is relevant because these parameters are always detectable in people infected with HIV, even if they take antiretroviral medication.
In addition, in one of the participants the viral antibodies had completely disappeared seven years after the transplant. According to Salgado, “this fact could be proof that HIV is no longer in his blood, but this can only be confirmed by stopping the treatment and checking whether the virus reappears or not.”
The only participant with a detectable HIV reservoir received an umbilical cord blood transplant – the rest was from bone marrow – and it took 18 months to replace all of their cells with the donor cells.
“This process can last from one to two months to more than a year, and we have observed that the shorter this period, the more effective the reservoir reduction is,” adds Kwon.
Another point of interest is graft-versus-host disease, which occurs when donor cells attack recipient cells. The only participant with detectable reservoir did not have this reaction.
“If we manage to control this effect so that it is not fatal,” says José Luis Diez-Martín, head of Hematology and Hemotherapy at the Gregorio Marañón Hospital and colleague.
Search for safer strategies than transplantation
These findings could be useful for the design of less complex and invasive HIV cure strategies, since stem cell transplantation has a high mortality rate and is only recommended in very serious hematological diseases.
“Our goal is to elucidate the factors that help to eradicate the virus after transplantation and then imitate them with alternative strategies safer than this intervention”, concludes Javier Martínez-Picado, ICREA research professor at IrsiCaixa and co-editor of the article.
Martínez-Picado is also co-director of the IciStem consortium together with Annemarie Wensing, clinical virologist at the University Medical Center of Utrecht (The Netherlands).
The next step will be to conduct a clinical trial, controlled by doctors and researchers, to stop antiretroviral medication in some of these patients and to provide them with new immunotherapies. In this way, it will be possible to check if there is a viral rebound and confirm if HIV has been eradicated from the organism.
Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant. Annals of Internal Medicine, 2018. doi: 10.7326 / M18-0759
Source: IrsiCaixa and Agencia Sinc