番茄社区

An oral abstract presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI) described the first case of a U.S. woman living with HIV-1 who is now in remission. The woman received a specialized stem cell transplant -- umbilical cord blood cells with a mutation protective against HIV-1 combined with stem cells from a related adult donor -- following an acute myeloid leukemia (AML) diagnosis. If HIV remission continues and she is determined to be cured, she would be only the third person to achieve cure, and the first HIV remission to have been successfully engrafted with umbilical cord blood cells.

番茄社区 brought together three expert leaders in their field -- moderator , of the University of California San Francisco, , of Emory University in Atlanta, and , of the University of Washington in Seattle -- for a virtual roundtable discussion on the issue of comorbidities and cure. This is the final of four exclusive episodes.

Following is a transcript of their remarks:

Gandhi: I think it would be good to change over to some comorbidities and cure, because if we look at the biggest news out of this meeting, I think the long-acting is going to get more and more attention, but we have to admit that the biggest, I think, attention grabber or the headline that came out the most was this possible third cure of, this time, a woman living with HIV.

And I don't know if anyone wants to start the discussion. I've talked to here in our division and tried to really understand what happened with this particular patient. But Carlos, I mean, even looking back at those two other cures we had, we have to remember that they were in the setting of HIV and essentially a blood cancer or lymphoma in the other two, where you had to do a transplant. And so here's a third transplant now that was required in a 59-year-old woman who has HIV and AML in this case.

del Rio: Well, that's exactly right. I mean, again, this is very exciting. And as I tell people, the science is incredibly cool. This is not something that has widespread applicability, but we're learning about cure by doing this study. So I think all these patients have had, as you say, a disease much more severe than their HIV. And in fact, the very famous Berlin patient, Timothy Brown, who was the first person cured by doing this bone marrow transplant using a donor that had the delta32 mutation in the CCR5, his leukemia recurred and he died of leukemia. He didn't die of HIV. So leukemia is much worse than HIV. And that's the reason why this woman was also transplanted. She would've died of leukemia had she not been transplanted.

What is interesting in this case is how they did it. What was different here is using cord blood for this. And they were able to then do it by taking cord blood from an infant that had the delta32 mutation, and then using that with a haploidentical transplant taking cells from an adult and combining them and doing that for the transplant. And what was fascinating here is not only the presence of the delta32, but the fact that this person did not have any significant graft-versus-host disease, which many people have said maybe is one of the reasons why people go into remission. And after they have stopped therapy -- we're 37 months post-transplant -- and this person is still virally suppressed. And, a lot of the mathematical modeling suggests that after 30 months, you're probably cured, but we still like to refer to that as remission. We still don't know if HIV is gonna come back or not. But again, very exciting, very interesting, but something that is paving the way to get better at our understanding, and eventually developing a cure. But clearly more science and science fiction than reality of something that we can go out there and implement.

Gandhi: This cord blood is really interesting, and I have no idea of the number of people who actually store their cord blood. And I don't know, Renee, if you have any sense of that, but it is sort of pluripotent. And so the idea was that ... there was first a grafting starting out with a 32-base pair deletion with some cells from a relative, because they needed relative cells, and then they did the cord blood with 32-base pair deletion. And maybe you don't react towards cord blood as much. Like you don't get mad at it. You know, you don't have this incredible graft-versus-host reaction that both the first two patients who were cured did. And there was a lot of speculation that that graft-versus-host reaction was required for the cure. But like you said, Carlos, it didn't seem to be required. She I think got discharged 2 weeks after a transplant, is doing really well, and then 37 months on ART [antiretroviral therapy] and then 14 months off.

I think it showed not just the potential of cord blood, but then this second thing is a woman. And, you know, there was this idea that it's gonna be harder to find matches with women. So let's see. I mean, I think you have to have leukemia or lymphoma. So the question is about gene therapy later to make this more widespread, not giving people transplants.

del Rio: Absolutely. And I think it's just fascinating. I think one of the issues that did come up, and some people ask, well why was this such a big deal? It was presented as a mixed-race woman, and a term that I don't particularly like, but I think what they were trying to tell us is the delta 32 mutation is very uncommon, but you see it in people, whites of Northern European descent, and the fact was she was not of Northern European descent. So this also talks about the fact that while this is not something that has high degree of ... this is not scalable -- a vast majority of our people living with HIV in this country are minorities, 40% of them are African American. And if you were just gonna say, well only people that can benefit from a delta32 transplant -- that essentially will only limit that therapy to whites, right? And by doing this, you're expanding it. So I think in a way this transplant, the way it was done also increases something that we didn't have before, which is a little bit of equity into the whole process.

Gandhi: And I think equity in terms of women, I think Rowena Johnson has looked at this from amfAR, but I think 11% of participants in cure trials are women. So that has been a major concern about the generalizability of strategies to women. So anything we can do, I mean, Renee, you work on this a lot, but the enrollment of women in clinical trials is a big issue.

Heffron: Yeah. I think it's just like you said, it's 11% in cure. I think it's 20% or 30% in treatment. And yeah, we have to do better to be more representative of all the people that need to benefit from the products being studied.

Gandhi: And include pregnant women, because that was the point that Dr. [Chloe] Orkin made in her plenary, which was something that we've been talking about now for years. Justify exclusion instead of justifying inclusion.

Heffron: And, get the safety data during pregnancy in parallel to the efficacy data on protection. So that when you go to your regulatory for approval or for decision about moving the product forward to licensure, you have that. And it doesn't need to be an exclusion.

Watch episode one of this discussion: Long-Acting Prevention and Treatment of HIV: CROI 2022 Part 1

Watch episode two of this discussion: Long-Acting Prevention and Treatment of HIV: CROI 2022 Part 2

Watch episode three of this discussion: Second-Line Dolutegravir for HIV Favorable to Other Boosted PIs

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