Continuing the Miracle of Healing, Interview with Dr. Christian Gaebler, Speaker of “The Next Berlin Patient” | AIDS 2024

Editor's note: At the just concluded 25th International Conference on AIDS (AIDS2024), as a major clinical research progress of the conference, Dr. Christian Gaebler from Charité – Universitätsmedizin Berlin, Germany, reported the case of the “Next Berlin Patient,” the seventh individual globally to be cured of HIV. Unlike the first “Berlin Patient,” this individual did not follow the traditional route of achieving a cure through a homozygous CCR5 Δ32/Δ32 stem cell transplant. Instead, this patient achieved a remarkable five-year sustained remission of HIV without antiretroviral therapy (ART) following a heterozygous CCR5 WT/Δ32 stem cell transplant. Infectious Diseases Frontier (IIDF)  sat down with Dr. Gaebler for an in-depth interview to explore the significance of this unprecedented case.

IIDF: Professor Gaebler, how does the “next Berlin patient” case you will discuss in your report differ or represent an advancement compared to the historical Berlin patient case?

Dr Gaebler: The biggest difference in our case is really that the next Berlin patient did not receive a homozygous delta-32 CCR5 transplant, but in this case had a donor, a heterozygous wild-type delta-32 transplant, and this was historically not believed to result in long-term remission. However, in this case, the patient decided to stop taking the antiretroviral therapy, and roughly three years after his allogeneic stem cell transplantation, we are now seeing a follow-up of close to six years without antiretroviral therapy, which was very surprising to us.

IIDF: What are the key immunological mechanisms underpinning the achievement of sustained HIV remission for over five years without antiretroviral therapy (ART) in patients who received CCR5 WT/Δ32 heterozygous allogeneic hematopoietic stem cell transplantation, as described in your research?

Dr Gaebler: This is really a very big question. First of all, we can say that right now, his HIV remission is not a result of immunological control. We are not seeing specific immune responses that would lead to control. The bigger question is where we need to look at immunological mechanisms in terms of the time after allogeneic stem cell transplantation to allow the depletion, or even potential eradication, of the HIV reservoir. We are still working on really understanding these mechanisms of how the donor’s immune system was able to deplete and have a meaningful impact on the HIV reservoir in the patient. That is the main question, and one we are still studying.

IIDF: Do you believe this treatment approach has the potential to become a viable path towards functional cure for HIV in the future? What are the primary challenges and obstacles that need to be overcome?

Dr Gaebler: I think this is really important because it really shifts our focus again on the HIV reservoir. This, again, is the biggest challenge. So what we need to do is really understand these mechanisms. If we can understand what was special in the donor immune system that led to these meaningful reductions in the HIV reservoir, this is something we could plan to emulate with other therapies. And I think this can really be done. Once we learn about it, one can think of other regimens – immunotherapies, antibody-specific and antibody-based immune therapies, and also therapeutic vaccinations – that can help us achieve some of the outcomes we have seen with stem cell transplantation.

IIDF: How have patient’s quality of life and safety been ensured during this period of prolonged HIV remission? Are there any long-term side effects or risks to consider?

Dr Gaebler: When we compare our case to previous cure cases, I think we can say that the stem cell transplantation itself was really successful and without a lot of adverse effects, even less than we had seen in other cases. However, stem cell transplantations are extremely intense treatments with high morbidity and mortality, so it is not a given that if this were to be repeated it would repeat itself in other patients. In our case, the procedure went well and has been in remission up til now, and on top that, we are seeing his cancer remission.

IIDF: In your opinion, what are the unexplored areas or emerging technologies that deserve attention for future research on HIV cure strategies?

Dr Gaebler: Again, it comes back to the HIV reservoir. We need to, first of all, have better tools to study the HIV reservoir. If we want to change something, first we have to be able to measure it, so we need HIV reservoir measurement tools. Then we need to find out out how to modulate the HIV reservoir, be it small molecules, be it immunotherapies, be it immunological mechanisms through, for example, therapeutic vaccination. These are the key questions we need to work on.

Background Information (Sourced from the Web):

The “Berlin Patient” refers to a German male who was diagnosed with both AIDS and leukemia in 2006. To treat leukemia, he underwent two stem cell transplants using cells from a donor with the CCR5 Δ32/Δ32 mutation. CCR5 is one of the main receptors through which HIV enters human cells, and the CCR5 Δ32/Δ32 mutation confers resistance to HIV infection. Remarkably, after the stem cell transplants, the patient’s AIDS symptoms completely disappeared, and HIV was undetectable for many years. This case is considered the first functional cure of AIDS in human history. Although this method of cure is not suitable for most HIV patients due to its high risk and complexity, it has provided important insights and clues for HIV cure research.

Since 2020, six additional HIV-infected individuals have achieved “cure” status:

1. The Berlin Patient: The world’s first person cured of HIV, diagnosed in 1995 and continuously treated with ART thereafter. In 2006, he was diagnosed with AML and underwent unrelated CCR5 Δ32/Δ32 matched stem cell transplantation the following year. HIV remained undetectable for 12 years, but he passed away from leukemia recurrence in September 2020.
2. The London Patient: Diagnosed with HIV in 2008, he underwent CCR5 Δ32/Δ32 stem cell transplantation in 2019 due to Hodgkin’s lymphoma, with no detectable HIV viral load since. A 2020 article in The Lancet confirmed him as the world’s second HIV-cured patient after four years of continuous follow-up.
3. The New York Patient: Underwent the world’s first cord blood stem cell transplant and achieved HIV remission in 2017. The case was initially disclosed in early 2022 and confirmed by a Cell publication in 2023. She remains the only known mixed-race female HIV-cured patient, suggesting that HCT treatment might offer cure strategies for different genders and races.
4. The Düsseldorf Patient: Diagnosed with AML in January 2011 and received CCR5 Δ32/Δ32 stem cell transplantation from a female donor two years later. HIV-1 virus was undetectable for nine years post-transplantation and four years after stopping ART. A 2023 Nature Medicine article confirmed him as the third person globally cured of AIDS.
5. The City of Hope Patient: Aged 68, diagnosed with HIV in 1988, and received CCR5 Δ32/Δ32 stem cell transplantation at City of Hope Medical Center in February 2019. HIV DNA was undetectable in peripheral blood and gut post-transplant. First disclosed in 2022 and confirmed by The New England Journal of Medicine in 2024, although still described as “long-term remission.” He is the oldest and longest-infected person among the cured or remission cases.
6. The Geneva Patient: Diagnosed with HIV in 1990, he received a CCR5 stem cell transplant at Geneva University Hospital in 2018 due to leukemia, with no viral rebound post-transplantation. The case was reported at the IAS HIV Science Conference in 2023.