Until 2019, the only case of HIV remission in the world was the man known as the “Berlin Patient”, Timothy Brown. He received in 2009 an allogeneic stem cell transplant due to an acute myeloid leukemia that he was suffering (Hütter et al., N Engl J Med 2009). The particularity of this transplant was that the cells came from an adult donor with homozygosis for the CCR5Δ32 mutation, which conferred resistance to the HIV infection by blocking the entry of the virus to the cell. After Timothy stopped cART, no HIV-1 RNA or HIV-1 DNA were detectable in peripheral blood, bone marrow or gut, and consequently it is considered that a sterilizing cure has been achieved (Yukl et al., PLoS Pathog 2013).
It took 10 years to be able to reproduce a case as the Berlin patient. Two new cases of HIV remission in London and Dusseldorf were described in 2019 (Gupta et al., Nature 2019; Jensen et al., CROI 2019). Those two cases have in common the CCR5Δ32 mutated donor with the Berlin Patient, an element that has been proved to be key in this process. Adam Castillejo and the Dusseldorf patients (whom identity is still unknown) have maintained undetectable viral loads after 4 and 3 years off therapy now.
All these three cases have in common that the allogeneic stem cell transplantation was performed in men receiving mobilized CD34+ cells from adult donors.
During the 2022 edition of the Conference on Retroviruses and Opportunistic Infections (CROI) has been presented the fourth individual with an HIV remission through an allogeneic stem cell transplantation by Yvonne Bryson from the University of California (Hsu et al., CROI 2022; Oral Abstract 65). This approach has two main characteristics that make it different from the previous ones: This is the first case of remission in a woman, and more important, it was achieved by the use of CCR5 mutated cord blood cells as a donor for the transplantation. The work described a mix-race HIV+ woman who received a transplantation with cord blood cells due to an acute myeloid leukemia in 2017. Three years after a successful transplant, she decided to stop treatment and after 14 months since there, no virus has been detected in plasma or cells from blood.
This is not the first attempt to achieve an HIV cure by using a mutated CCR5 cord blood donor in allogeneic stem cell transplantation, although in a previous case a full remission of the hematological disease was not possible (Duarte et al, Lancet HIV 2015).
The study opens the door to use cord blood units for future transplantations in HIV+ individuals that require it, always after suffering a hematological disease. This could be advantageous since cord blood transplants require lower similarities in the HLA match, what give more opportunities to find compatible CCR5 mutated donor. However, the low dose of cells from these donor units with the delay in reaching the full donor chimerism associated to this type of transplant, have moved the balance to preferentially use adult donors to increase the chances of a successful transplant.
These new results also give importance to the new gene therapies under investigation that aim to disrupt the CCR5 receptor in HIV+ individuals, the factor that has been key in all the cases of HIV remission.
María Salgado PhD.
AIDS Research Institute IrsiCaixa
Hospital Germans Trias i Pujol