The first two cured patients (unsure about the third) were also cured by a similar bone marrow transplant from a resistant donor (and I think leukemia was also present?). This is good news, as validation of the other cases, but it still remains an infeasible path for the vast majority of HIV positive people.

True. But maybe additional confirmation that this pathway really works will help spur research into a way to replicate the same effect, without requiring the full bone marrow transplant process?

> But maybe additional confirmation that this pathway really works will help spur research into a way to replicate the same effect, without requiring the full bone marrow transplant process?

Doubtful. It's been known for a long time that the CCR5-delta 32 mutation conveys HIV resistance because it results in a different CCR5 coreceptor which HIV uses to enter white blood cells (this is the whole reason the bone marrow donor was selected in the first place).

Thus, the bone marrow transplant process works because now ALL of this patient's cells have that different, resistant CCR5 coreceptor. Hard to imagine a way to replicate this process without some method that results in all new white blood cells being generated like this.

Genetic modification delivered via mRNA? There are some biohackers that do that sort of stuff, so it would imply at least some feasibility

Fair enough.

What makes HIV hard to eliminate is that it persists in bone marrow. What's happening in these transplants, in cancer patients who also have HIV, is that the patient's original bone marrow (having become cancerous) is killed off and completely replaced, taking the HIV with it. And killing off the original bone marrow is the nastiest part of the procedure by far (source: my uncle went through it) -- but that's what gets rid of the HIV. Anything that replicates that effect would be an alternative transplant process, not an alternative to one.

> What's happening in these transplants, in cancer patients who also have HIV, is that the patient's original bone marrow (having become cancerous) is killed off and completely replaced, taking the HIV with it.

That's not accurate. If that were the case, then ANY bone marrow transplant could potentially cure an HIV patient. What's happening is that bone marrow is what generates white blood cells, and the donor in this case was naturally resistant to HIV due to the CCR5 delta 32 mutation. This results in white blood cells that HIV can no longer easily enter.

So what's happening is ALL of the patient's white blood cells are being replaced (rather, generated by this new donor marrow) with ones that are resistant to HIV.

What stops us from inducing a CCR5 delta 32 mutation in hiv infected people?

What process do we have to reliably mutate every single cell of certain types in bone marrow, with only a desired mutation and no other?

a modified HIV vector?

DNA Vaccines?

We don't have a process to do what is described.

Even if a small amount of unmutated cells remain that still means that the person is cured of HIV right? Though they may still be infectious

Thanks for the correction.

So bone marrow transplant from someone with natural resistance (the same gene as the Chinese CRISPR kids?)?

Wouldn’t this have happened by chance before 6-7 years ago when the first case was reported?

They couldn't do it at all until they had really good HIV-suppressing drugs. You won't do a transplant into somebody with an active HIV infection.

They still won't do it if they can avoid it. This an extreme measure, killing off the entire immune system and replacing it. They still need to find a donor who is sufficiently compatible, and then has the right set of genes.

So it just took time for all of the pieces to fall into place.

Use this to treat diabetes type one, do a pancreas transplant and replace the immune system so it does not reject the transplant.

Usually, just the transplant part is sufficient. https://connect.mayoclinic.org/blog/podcasts/newsfeed-post/h...

It's mentioned in the comments of the article, but "just the transplant" is not really enough. You still need heavy immune suppressants, which is rarely worth the side effects.

That would be fantastic, but there are enormous tradeoffs. This is massive, massive surgery that comes incredibly close to killing the patient.

They are unlikely to do it if the disease can be controlled with an insulin pump, which is far less invasive. Insulin pumps are far from perfect solutions. (Somebody close to me has one and I can observe what a massive pain in the ass it is, among other places.) But surgery like this is going to have to come a long way before it's routine enough to replace a therapy that is aggravating but sufficient.

I'm guessing that HIV positive patients who also develop a type of cancer that can receive bone marrow transplants as treatment are rare. Bone marrow matches are extremely rare. Add to that: bone marrow matches with the particular mutation (CCR5-delta 32) can only compound that rarity. All this adds up to poor odds.

Indeed. But rapid advances in genetic therapies mean it may someday be possible to 'upgrade' a patient's existing marrow in-place, with just the necessary new genes.

How can they claim a cure for a retroviral infection, which rewrites host genomes in cells? They can claim to obtain significant purge of cells with rewritten genomes?

I'm missing some fundamental explanation where the rift between soundbites and science seems large.

The bone marrow transplant is from a person with a gene that makes their white blood cells resistant to the virus. Once the person's old WBCs are gone (killed by chemotherapy in the case of leukemia patients, which, IIRC, all these patients were due to the danger inherent in bone marrow transplants), the new bone marrow then produces only resistant cells.

so that presumes HIV didn't infect any other reproducing cells?