Q&A: Seventh case of potential HIV cure comes with a twist
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Key takeaways:
- Another person has potentially been cured of HIV following a stem cell transplant from a donor with a rare genetic mutation.
- The mutation makes a person naturally resistant to HIV infection.
A seventh person has potentially been cured of HIV after receiving a stem cell transplant to treat blood cancer, researchers announced on the eve of the 25th International AIDS Conference.
The 60-year-old German man has remained free of detectable HIV for almost 6 years since stopping ART in September 2018, which was around 3 years after he received the stem cell transplant for acute myeloid leukemia, according to Christian Gaebler, MD, MSc, professor of translational immunology of viral infections at The Charité medical university and hospital in Berlin, and colleagues.
Gaebler and colleagues have dubbed the man the “next Berlin patient” — a reference to Timothy Ray Brown, the first person ever cured of HIV after undergoing a stem cell transplant. Brown remained in treatment-free HIV remission for more than a decade until his death in 2020 following a recurrence of leukemia.
One important aspect of the new case sets it apart from the rest, however.
Most of the other patients, including Brown, received stem cells from a donor who harbored two copies of a rare genetic mutation that makes people naturally resistant to HIV —meaning both of the donor’s parents had the mutation.
“We call those people homozygous, and they are essentially immune from infection with HIV,” International AIDS Society President Sharon R. Lewin, PhD, explained to reporters.
Unlike Brown and most of the others, the newest case involved a transplant from a heterozygous donor — someone with only one copy of the mutation, called CCR5-delta 32, which prevents HIV from entering human cells. This means it may be possible to cure HIV with a stem cell transplant from a donor with only one copy of the mutation, Gaebler said.
As the case of the “Geneva patient” demonstrated last year, it also may be possible if the transplant comes from a donor who does not have the mutation at all.
Despite these cases, experts have cautioned that stem cell transplantation is not a scalable cure for HIV — it is too risky and expensive to be considered a viable option for all patients. What does the new case add to the conversation? We spoke with Gaebler to answer some of our lingering questions. His answers have been edited for length and clarity.
Healio: Do you consider this patient to be cured?
Gaebler: I think we have to say it’s a potential cure. In all of these cases, we can never be 100% sure. What’s remarkable in our case is that we’re seeing this after almost 6 years now in remission, keeping in mind that we have these somewhat unusual circumstances that we haven’t seen in the past. While we cannot be certain, we haven’t found any HIV reservoirs, which also doesn’t mean that they’re not there.
Healio: In your opinion, how likely is it that this patient who has been in remission or potentially cured for almost 6 years now would rebound?
Gaebler: That’s hard to tell. We’ve been discussing this internally, and also with other people in the HIV field. I think if he had a donor graft with a [homozygous] CCR5 mutation, I would say the chances are likely zero. In our case, knowing that there is functional CCR5, and maybe there could potentially still be a cell carrying a provirus there, it’s not zero.
But just looking at what we know about viral rebound dynamics, in a functional donor graft with functional co-receptors, we would expect a much shorter time to viral rebound — probably weeks to months, something like that. So, I think the longer we’re seeing it, the more confidence we get that, most likely, we won’t see a viral rebound.
Healio: Taken together, can all of these cases tell us anything about the search for a scalable HIV cure?
Gaebler: What makes me so interested in this case is that it shifts our focus a little bit away from the CCR5 mutation toward the mechanism of reservoir depletion, which most likely is mediated through allogenic immunity. So, the donor transplant is not only targeting leukemia cells, but also replacing these latently infected cells that form the HIV reservoir.
What I’m thinking right now is that the main driver in this and the other cases must have been allogenic immunity.
Of course, the therapy is not scalable. However, just knowing that we can eradicate these reservoirs gives us the proof that it’s possible. By learning from the cases, it gives us a chance to hopefully translate them into a more scalable approach.
Healio: Is there anything else that sets this case apart from the other ones?
Gaebler: Not only was the transplant heterozygous for CCR5, but the patient also was one of these extremely rare individuals. In Europe, around 16% of individuals are heterozygous for the delta 32 mutation. We’re interested in understanding if this might have played a role on top of them getting the heterozygous transplant. Timothy Brown was also heterozygous before receiving a delta 32 homozygous transplant.
Healio: If you’re a patient with HIV or a clinician who is treating patients with HIV, is there a reason for hope when you read about these cases that there will eventually be a cure?
Gaebler: I’m very optimistic that there will be eventually a cure. I was asked before if we’re putting too much emphasis on these cure cases. I don’t have a good answer for that. For me personally, as a scientist, by seeing that these cases are possible, it does give me hope. My feeling is that the community feels the same way.
But I also agree that we shouldn’t overpromise, and we need to be careful that we’re not taking away thunder from all the other exciting science that is going on. We’re making major strides, not only in this regard, but we’ve seen long HIV remission with passive immunotherapies. So, we’re not only looking at stem cell transplants, but we’re really making progress on many ends. I hope by bringing them together and integrating all of these really good scientific advances, we will be able to find a cure.
Reference:
- Gaebler C, et al. Abstract 12163. Presented at: International AIDS Conference; July 22-26, 2024. Munich.
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