In this observational study
we aimed to investigate the HIV eradication mechanisms that can be related with
allogenic stem cell transplantation, with the ultimate goal to design new strategies for HIV eradication.
Our results show how
different transplantation-associated factors as the stem cell source, the conditioning regimen or the graft-versus-host disease
might contribute to HIV eradication.
There's just one case of complete HIV eradication in the world.
Timothy Brown, known as "The Berlin patient".
A HIV-positive man who received two stem cell transplants to treat an acute myeloid leukemia.
The donor had a mutation called CCR5 Delta 32 on CD4 cells
making them nearly immune to HIV because it averts the virus to enter the cell.
Brown stopped taking HIV medication and today, 11 years later,
virus is no longer found in his blood.
Our hypothesis was that, in addition to the CCR5 Delta 32 mutation,
other transplant-associated mechanisms had a strong influence on HIV eradication.
To study that, we constituted the IciStem consortium
in 2014, with funding from the Foundation for AIDS Research, amfAR.
This study included six participants who had survived more than two years after
transplant from CCR5 wild-type donors.
We excluded donors with CCR5 Delta 32 mutation
to focus on other conditions.
All participants achieved remission of their
hematological disease, no longer had immunosuppression and maintained
antiretroviral treatment during and after transplant.
After the transplant, 5 of 6 participants had undetectable reservoir in blood and tissues.
The only participant with a detectable HIV reservoir received a cord blood transplant,
did not developed graft-versus-host disease
and had mixed chimera in T-cells up to month 18 post-transplant.
In one of them, we did not detect any viral antibodies by month 88
suggesting that he experienced seroreversion.
This suggests that what we call graft-versus-HIV reservoir disease might be key for the HIV eradication
by the replacement of the recipient cells with the new cells from the donor.
This information will be useful to allow the development of less invasive strategies to eradicate HIV infection,
since the stem cell transplant presents a 50% mortality ratio and is just recommended in life-threatening