The "Berlin patient", nickname by which Timothy Ray Brown is known, is the first human being in history to beat 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, US researchers presented at the Conference on Retroviruses and Opportunistic Infections (CROI2022) the third known case of remission: that of a New York woman.
What do these three people have in common?
That all of them received treatment with cells that were resistant to HIV infection due to a very specific but rare mutation.
For this reason, some experts consider that these three experiences demonstrate that Acquired Immunodeficiency Syndrome (AIDS), the final stage of HIV infection, could become a curable disease in the very near future if this therapy is generalized.
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 bone marrow transplant as part of hematopoietic stem cell treatment 12 years later.
He had assumed that his was a chronic disease, but, to everyone's surprise, after the operation the symptoms of immunodeficiency disappeared.
He was even able to abandon 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 quasi-species of R5 virus.
They are so named because they use a "lock" called the CCR5 receptor to enter CD4 T cells.
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, Brown 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, an acute myeloid leukemia was detected 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 an HIV-positive Londoner.
But they found a wonderful “side effect”: the virus disappeared.
And after 18 months without antiretroviral medication, he showed no trace of the AIDS-causing virus in his body.
Does that mean that cell transplantation is the solution?
Not necessarily.
On the one hand, because, according to the same IciStem researchers, it is a very aggressive strategy, with a mortality rate of 40-50%.
And on the other, because there is still a long way to go before proving its effectiveness.
Published data suggest that there are ways to achieve complete remission of HIV and it could be achieved in a non-aggressive way
Without going any further, in 2014 the case of another man known under the pseudonym "the patient from Essen" was reported who, despite receiving a similar transplant, experienced a rapid rebound effect or rise of the virus while he was without antiretroviral treatment .
Finally, he succumbed to a recurrence of a lymphoma that he suffered from.
This same effect was observed in three other patients after stopping 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.
To date, IciStem has performed some 40 transplants in individuals with hematologic 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 New York woman (also a transplant recipient) has yet to 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 people 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
is an associate professor at the Faculty of Medicine of the University of Vic – Central University of Catalonia.
This article was originally published on The Conversation.
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