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The “Berlin Patient”, nickname by which Timothy Ray Brown is known, is listed as the first human being in history to defeat the Human Immunodeficiency Virus (HIV) in 2017.
And it is not an isolated case. In 2019, another case of virus eradication was revealed, that of Adam Castillejo, a Venezuelan who became known as the “London Patient”. And in early 2022, American researchers presented at the Conference on Retroviruses and Opportunistic Infections (CROI2022)the third known case of remission: that of a woman from New York.
What do these three patients have in common? That they all received treatment with cells that were resistant to HIV infection due to a mutation Very specific but rare. That is why some experts consider that these three experiences show that the Acquired immunodeficiency syndrome (AIDS), the final stage of HIV infection, could become a curable disease in the very near future if this therapy becomes widespread.
However, as we will see below, there are other data that cast certain hints of doubt on this forecast.
The “Berlin Patient”
HIV is a retrovirus that completely destroys the immune system of infected people. Currently, antiretroviral drugs manage to control the replication of the virus and the progression of the disease, but not cure it.
Timothy Ray Brown, an American living in Germany, was diagnosed with AIDS in 1995 and received a kidney transplant. bone marrow as part of a hematopoietic stem cell treatment twelve years later. She had assumed that hers was a chronic disease but, to everyone’s surprise, after the operation they disappeared the symptoms of immunodeficiency. She was even able to stop taking antiretroviral drugs – under strict medical supervision, yes – because there was no longer a trace of HIV in his body.
His body had apparently acquired resistance to any subtype or quasispecies of R5 virus. They are so called because to enter the lymphocytes T CD4 use a “lock” called the CCR5 receptor. However, there was still the possibility that another subclass of the virus, the X4 virus, could infect it due to the existence of an alternative entry called CXCR4. Therefore, as a preventive measure, Timothy continued to take daily treatment to reduce the risk of reinfection with HIV.
Sadly, fate had another trick in store for him. Months after overcoming AIDS, a myeloid leukemia sharp that ended up killing him in 2020.
The “Essen Patient”
An international consortium called IciStem studied the second case of HIV remission after receiving a transplant of cells with the CCR5 Δ32 mutation due to Hodgkin’s lymphoma. The treatment was intended to cure lymphoma in a London patient. But they found a wonderful “side effect”: the virus disappeared. And after 18 months without antiretroviral medication, she showed no trace of the AIDS-causing virus in his body.
Does that mean the cell transplant it’s the solution? Not necessarily. On the one hand because, according to the IciStem researchers themselves, it is a very aggressive strategy, with a mortality rate of 40-50 percent. And on the other because there is still a long way to go before proving its effectiveness.
Without going any further, in 2014 the case of another man known under the pseudonym of “The Essen Patient” who, despite receiving a similar transplant, experienced a rapid rebound effect or surge of the virus while he was without antiretroviral treatment. Finally, the patient succumbed to the recurrence of a lymphoma that he suffered from.
This same rebound effect was observed in three other patients after suspending their antiretroviral medication, although in these cases the failure could be due to the fact that they received cells without the CCR5 Δ32 mutation.
The future of the fight against AIDS is bright
The good news is that there is hope. According to the IciStem researchers, the published data suggests that there are ways to achieve a complete remission of the virus. And they trust that it could be achieved in a non-aggressive way. Till the date, IciStem has carried out about forty transplants in patients with hematological disease, of whom nine previously had the CCR5 mutation. At least half of them survived the year after transplant without stopping taking antiretrovirals.
Meanwhile, the patient New York (also transplanted) still does not experience viral rebound. She is seronegative for HIV antibodies and her leukemia continues to regress.
We will have to wait for new follow-up data on these patients to reach more reliable conclusions about these possible cures and confirm that there is a direct cause-effect association and that they are not mere coincidences.
If it is possible to clarify the mechanisms behind the elimination of the virus in these transplant patients and the results are reproduced through interventions directed against CCR5 with less risk but more effective and sustainable over time (vaccines with latency reversing agents, neutralizing antibodies and gene editing, among others), we may be able to subdue HIV once and for all.
Santiago Roura Ferrer, Associate Professor Faculty of Medicine, University of Vic – Central University of Catalonia.
This article was originally published on The Conversation.
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