HIV Cure Via Cord-Blood Stem Cell Transplant

A New York woman may be the first to have been cured using a new paradigm of treatment.

F. Perry Wilson, MD MSCE
6 min readMar 16, 2023

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From 1981, when the first patients with HIV were identified, to 2007 — a cure for the deadly virus would have been a miracle. And then, Timothy Ray Brown — known as “The Berlin Patient” was cured. And just like that, a miracle became science.

Mr. Brown had been diagnosed with HIV in 1995. In 2006, he was diagnosed with acute myelogenous leukemia which would require a donor bone marrow stem cell transplant for treatment. But this wasn’t just any donor. His donor was one of less than 1% of the world’s population, with a unique genetic mutation known as the CCR5-∆32 mutation. This rendered the donor’s immune cells resistant to HIV.

It was a gamble, to be sure, but it proved to be a successful one. Mr. Brown lived from 2007 to 2020 without the need for anti-retroviral therapy. He died from a relapse of AML. No HIV was detected at the time of his death.

The question, of course is simple: why can’t more people be cured of HIV?

Let’s state the obvious first. Curing HIV with a bone marrow transplant is a bit like swatting a fly with a sledgehammer. In an era where anti-retroviral therapies are highly effective and can lead to essentially normal life-expectancy, undergoing a procedure involving high-dose chemotherapy, radiation, stem cell transplant, and lifelong immunosuppression does not exactly minimize the risk-benefit ratio.

So to date, all cases of HIV cure via bone marrow transplant — and there have been perhaps 5 — have been in the context of bone marrow transplant for some other disease — leukemia or lymphoma.

The reason for the vanishingly small numbers here are not simply that bone marrow transplants are rare. The stars really need to align for these patients because not only do they need to find a suitable donor, but they need to find one who carries the CCR5-∆32 mutation. Which means take the number of eligible donors you may have for a bone marrow transplant — already a very small number — and divide it by 100.

And, by the way, if you are of non-European ancestry, your chances are even lower. People of non-european ancestry are substantially under-represented in bone marrow registries in the first place. They are also less likely to have that particular beneficial mutation. Needle in a haystack doesn’t do this justice. We’re talking a needle in a field of haystacks.

But the stars might not need to align quite as perfectly anymore, thanks to research presented in this paper, appearing in Cell, that shows what appears to be the first HIV cure that is a result of cord-blood derived stem cells.

The woman described in the manuscript, being treated for leukemia, characterized herself as mixed-race — which already makes the chance of finding a suitable bone marrow donor low. But a donor was found — matching in 8 out of 8 haplotypes — the proverbial needle in a haystack. But, this donor, like the vast majority of us, had the normal CCR5 gene, not the HIV-resistant version.

This is where it gets clever. The researchers had been screening cord blood registries for samples with the HIV-resistant mutation. Out of 18,000 samples, they found 171 with the beneficial mutation. One of those 171 was a 5 out of 8 match for the patient in this study. And that’s ok — because prior research has shown that cord blood transplants fare better in the context of HLA-mismatch compared to traditional bone marrow transplants.

The patient was exposed to high-dose chemotherapy, radiation, and other treatments to eradicate her own immune cells, and given both the adult donor and the resistant cord blood samples. The researchers believed the adult cells would support the immune reconstitution as the cord blood cells slowly took over.

And they were right.

This graph shows where her white blood cells were coming from after the transplant over time. At first, the adult donor cells predominate, but by 14 weeks, her immune system was entirely repopulated by those cord blood cells — those cells that were resistant to HIV.

Source: Cell

The patient recovered from the procedure and remained on anti-retroviral therapy for about 3 years. Viral load was fully suppressed throughout that time. And then, in careful discussion with her doctors, she stopped the anti-retrovirals.

And the viral load remained suppressed. It’s been two years with no viral load off any anti-HIV therapy.

Source: Cell

The researchers weren’t content to only look at viral load though. After all, individuals on anti-HIV therapy often have undetectable viral loads and we don’t call them cured because there are viral reservoirs in the system.

They used the quantitative viral outgrowth assay (QVOA) to search for those reservoirs. As you can see here, there weren’t any.

Source: Cell

In a petri dish, they added live HIV virus to the patients new immune cells to see if they would get infected. Control cells were rapidly invaded. The patient’s cells? Nothing.

Source: Cell

They even tested the cerebrospinal fluid since some studies have suggested that the nervous system can be an HIV reservoir. Nothing there either.

Of course, we might be premature calling this a cure. Time will tell how durable this remission is. But the bigger picture here is the opportunities this study opens up.

Cord blood has multiple advantages over adult-derived bone marrow stem cells. Harvesting cord blood is painless and safe. Cord blood transplants have less graft-versus-host disease. In contrast, the “be the match” bone marrow registry has 22 million individuals in it who could be called up to donate bone marrow — largely of European ancestry. A white person has a 77% chance of finding a donor in the registry. A black person only a 23% chance.

22 million people in the international bone marrow registry. That’s great. But that many people are born every two months. And cord blood can be taken on the spot — no need to call donors later. The possibilities for cord blood are staggering. And while it may start with the rarest of rare cases — a patient with HIV, and a cancer amenable to stem cell transplant, where it will end may be transformational.

A version of this commentary first appeared on Medscape.com.

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F. Perry Wilson, MD MSCE

Medicine, science, statistics. Associate Professor of Medicine and Public Health at Yale. New book “How Medicine Works and When it Doesn’t” available now.