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I've had an allogenic stem cell transplant. It was hell. I no longer have cancer, so it was worth it. But HIV/AIDS (with standard treatment and testing) no longer significantly reduces life expectancy.
I have a hard time imagining a future where allogenic stem cell transplants are used to treat HIV. The procedures are incredibly risky and carry long term consequences (and in many cases, like mine, also unbearably painful for weeks).
To me, the most likely practical consequence of these findings is to spur on interest in using CRISPR (or other in-vivo genetic modification strategies) to alter the genome of an HIV patient to be "immune" to HIV. (A similar idea is used in treatment of some blood cancers. Chase the rabbit-hole of "CAR T Cell therapy" to get started.)
This explanation for the technique’s general inapplicability is touched on in the article.
It sounds like all of the HIV-cured were people that had a blood cancer that was, presumably, not responding to chemo, and for which they needed to get a new blood-making system grafted in. And, since this extremely risky procedure was a sunk cost, they rolled in the stem cell donor having an HIV resistant mutation as a might-as-well-since-we’re-in-there freebie while treating the blood cancer with a last ditch effort.
Inducing the HIV resistant mutation by other means is clearly the general way to go.
Finding an optimal donor match (via HLA typing) rarely returns many "perfect" matches. Perhaps there are systems that record both the CCR5 mutation and HLA typing, but I'd expect most donor matches, found via registries like https://bethematch.org/, will not have that information available.
I haven't dug into the weeds here (and, for personal emotional reasons, I will not), but I find it hard to believe the medical staffs would have seriously considered "can we find a donor that matches AND will possibly cure the HIV". The diagnosis-to-death timeline for many blood cancers is fast when other treatments don't work. Delaying a transplant by 2 weeks in order to find a slightly more optimal donor seems crazy. (Though I suppose the after-transplant care for someone with HIV might be trickier than those without HIV. But patients will be immune-compromised for at least months post-transplant, so maybe HIV isn't that big of a deal.)
HIV, in rich countries at least, is a managed condition these days. I'd imagine the only issues would be any sort of interactions between the don't-get-AIDS cocktail and the cancer drugs.
Perhaps the matching system has more data in Germany, or perhaps they really are just writing up happy accidents in which they discover that the patient lucked into a CCR5 donor and also already had low enough levels of HIV that the operation made a difference.
> I find it hard to believe the medical staffs would have seriously considered "can we find a donor that matches AND will possibly cure the HIV".
According to a report of the Tagesschau (belonging to the German public television chanel ARD),[1] the patient had leukemia and the doctors were looking for a fitting donor who was also missing a so-called CCR5 co-receptor. According to the report, people having such a gene mutation can be found especially in Central and Northern Europe.
The patient had already been treated in 2018, but is only now considered cured because he has not experienced any HIV symptoms since then.
I do not know whether it was relevant in this case, but Germany has a Central Bone Marrow Donor Registry with currently almost 10 million people registered.[2]
[1] See https://www.tagesschau.de/wissen/gesundheit/hiv-leukaemie-st... (in German)
[2] See https://www.zkrd.de/neue-spender-weiterhin-gesucht/ (in German)
I read a little about allogenic stem cell transplants and it really sounds risky and more of a last chance type option.
"Last chance" describes both the way it was introduced to me by my medical team, and the circumstances around my SCT. I don't know how factually accurate it is, but my medical team had said there's about a 30% mortality rate caused by the SCT within about 90 days. (And, prior to chemotherapy ceasing to work, I'd been repeatedly reassured by medical staff with "chemo sucks but it isn't gonna kill you like a stem cell transplant would!")
Not endorsing the credibility of this article, but if you think this is interesting, you'll likely think https://www.variantbio.com is awesome.
They scour the globe looking for people groups, families, regions, etc. that have extremely rare immunities and other outlier characteristics in order to sequence their DNA.
> The stem cell transplantation is a complicated procedure that comes with many risks, and it is too risky to offer it as a cure for everyone with HIV.
Maybe it's just me but I hate when people/articles generalize like this. What are the risks? What are the benefits? What is the SPECIFIC hazard to health that is occurring? They just stick to general statements, because, in my opinion, they don't want to do the research. Either way the news itself is good to hear.
Stem cell transplantation is usually performed by bone marrow transplant, which is a pretty risky procedure: it involves destroying the recipient's own bone marrow to introduce the donor bone marrow, which can leave the recipient without significant numbers of white blood cells for a while, making them extremely vulnerable to infection.
In contrast, HAART for HIV is far less risky and far more safe, allowing people with HIV to live basically a normal life as long as their viral loads stay at undetectable limits.
That's the received wisdom, but it really seems trite.
HAART leaves people extremely vulnerable to infection as well, after all. The difference is that HAART means that point will come at some unpredictable point in the future, whereas a bone marrow transplant makes the window more predictable. And beyond that, it fails to consider the risks of decades of really toxic medication.
Is a bone marrow transplant really worse than decades of liver damage followed by developing AIDS eventually anyway?
Maybe, maybe not, but dismissing the heavy questions of a persons life with "basically normal" is not helpful.
The article also does not mention the type of transplant: autologous or allogeneic.
As a recipient of an auto-transplant as part of cancer treatment, I perhaps can speak to the complexity of the procedure and the risks. For certain types of lymphomas, the best chance for life-long remission is through a stem-cell transplant.
- The patient first undergoes conventional chemotherapy to attempt to achieve remission.
- The patient then performs a barrage of tests to ensure that they are healthy enough to withstand the transplant procedure.
- The patient has a Hickman catheter installed. The catheter is a device with tube into the superior vena cava (one of the main return veins into the heart) and two external ports for drawing and returning blood and administering fluids and drugs.
- The patient performs mobilization and collection. During mobilization, the patient self-injects a growth factor drug that causes the body to produce extra hematopoietic stem cells and release them into the blood stream. During collection, the patient is connected to a centrifuge machine and the stem cells are collected and preserved.
- The patient enters the hospital for the transplant procedure. High dose chemotherapy is administered. For cancer treatment, the purpose of the chemotherapy is to destroy any cancer cells remaining in the body. Even though the patient may be in remission from first-line chemo, some cancers can return from just a few remaining cancer cells. A side-effect of the high-dose chemotherapy is the destruction of the body's ability to produce blood.
- After chemotherapy, the patient's own stem cells are injected. Within 7 to 10 days, these cells will recolonize the bone marrow, "engraft" and begin producing blood.
- Once the patient's blood cell counts are on the rise and the patient is otherwise stable, he is sent home. The patient typically needs live-in care at home for about 30 days (the patient's blood counts are still very low and a normally trivial injury from cooking or cleaning could be deadly).
The risks of the procedure are from the high-dose chemotherapy and the fragile state of the immune system after the transplant. After a transplant, _all_ immune memory is erased and the patient is as a newborn as far as immune system capability is concerned.
The risks include:
- Chemo related organ damage to heart, lungs, kidneys and liver.
- Chemo-induced pneumonitis.
- Graft failure (e.g. failure of the stem cells to recolonize the bone marrow).
- Infection (since the immune system is destroyed during the process, a normally minor infection can be deadly).
According to my transplant doctor, the auto-transplant process has about a 2% risk of death.
The benefits are that the probability of a cancer relapse is significantly reduced (say 90% risk to 50% risk).
For the patient, the process is very difficult and recovery time is approximately one year.
(edited for formatting)
All four of these patients had undergone stem cell transplants for their blood cancer treatment. Their donors also had the same HIV-resistant mutation that deletes a protein called CCR5, which HIV normally uses to enter the cell. Only 1% of the total population carries this genetic mutation that makes them resistant to HIV.
The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS.
A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. [1]
Why this treatment still worked is because:
However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another co-receptor (CXCR4), but persisted in using CCR5: they either bound to alternative domains of CCR5 or to the receptor at a higher affinity. However, because there is still another co-receptor available, it is probable that lacking the CCR5 gene does not make one immune to the virus; it would simply be more challenging for the individual to contract it. [1]
So a mixture of anti-retroviral treatments, which suppress the HIV replication to a point of not showing up in PCR tests anymore (while taking the medication), and (partially?) inhibiting the remaining viruses from infecting cells via the CCR5 pathway, further limiting their replication, caused these patients to be cured.
I don't know if the replication slowed down so much that their body was able to kick HIV out once and for all, or blocked it outright because the already reduced number of viruses simply could not beat the odds of infecting via a alternative pathway. Kudos to the researchers!
Why is this important: The CRISPR babies[2] had this exact gene removed, and everybody claimed that he cured them from ever getting HIV, even though it's simply not true.
Note that there are also drugs which disable CCR5, without gene modification (Selzentry).
[1] https://en.wikipedia.org/wiki/CCR5 [2] https://en.wikipedia.org/wiki/He_Jiankui_affair
It's been a few years now but I used to work on research on this particular alternative receptor.
To handwave and simplify a bit CCR5 is the dominant pathway for the virus to spread in a healthy patient. HIV tends to mutate in patients from attaching to CCR5 (called phenotype R5) to CXCR4 (called X4) once the immune system is weaker. Patients with the X4 are not as infectious as a healthy immune system can fend it off.
So CCR5 is more or less the only pathway for the virus to infect a healthy host, as far as I can remember.
Your quoted line from the article stated: "Their donors also had the same HIV-resistant mutation that deletes a protein called CCR5, which HIV normally uses to enter the cell. Only 1% of the total population carries this genetic mutation that makes them resistant to HIV."
Then you stated: "The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS."
I'm not quite sure how you made the leap from "... which HIV normally uses to enter the cell" to thinking the article stated "... CCR5 being the only pathway of the HI Virus to infect your cells", but :shrug:
Your right, horribly is probably the wrong word, but the same quote said [..] this genetic mutation that makes them resistant to HIV.
I don't care so much about the wording in this article, but there have been a lot of efforts for HIV "cures" in the direction of disable CCR5 = disable HIV, which unfortunately is not true.
Also when you disable CCR5 on more and more people, the selective pressure may evolve to HIV which primarily targets CXCR4.
The way seems to anti-retroviral drugs, and then finish it with CCR5 inhibition.
>The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS.
I think the article was just simplifying a very difficult topic in order to reach a mass audience. Very enlightening information that you've added to more illuminate the topic, so chapeau.
From wiktionary[0]:
> chapeau (interjection) - well done, a verbal representation of a hat tip
Don't go to wikipedia[1], or else you'll be confused by "A chapeau is a flat-topped hat once worn by senior clerics."
Thanks for the new word, justinator!
Despite all the caveats and potential inaccuracies of the article, what a time to be alive!
> Only 1% of the total population carries this genetic mutation that makes them resistant to HIV.
Wow, I didn't even know that you can be immune to HIV. It's only a matter of time before we have technologies to change our genetic code or at least the genetic code of two cells before they form an embryo.
> It's only a matter of time before we have technologies to change our genetic code or at least the genetic code of two cells before they form an embryo.
I suggest watching the movie 'Gattaca' ;-)
Seriously though, it is really good
> Wow, I didn't even know that you can be immune to HIV.
HIV contains some code which use to convert a cell to be a zombie (afaik that cell's vulnerable place in cell's DNA is called CD4). But some people has that part of cell's DNA slightly different, not better not worse but different, therefore not vulnerable to that special code. The HIV for different cells is yet to be discovered.
When we will have understanding of how to change the DNA code (implementing is really easy tbh), than any malintentioned person might develop new viruses shaping some known ones to be even more destructive.
Aren't we there yet? Gain of function research is exactly that and it gave us COVID
Read my comment above, CCR5 gene deletion/mutation does not make you resistant to HIV, it can also infect via CXCR4
Recently there was a post on HN about some child whose genetic disease was cured by inserting DNA (can't remember the specifics). I wonder if something similar could be done with HIV. Obviously you'd have to insert a mutation for the CCR5 protein. Then the problem is you have all this bone marrow that's still producing white blood cells of the old type, so you'd need some way of killing off the old bone marrow cells without the right mutation and replacing them with the new ones.
Nice, but I wonder how long before it's going to be an option for all those who want it (even ignoring whether managing HIV may be better then curing it).
I'm still waiting for ocumetics bionic lenses to end glasses and contact lenses (ha ha ha, they're probably still collecting money from all the parties they should be destroying) and I lost hope we'll ever see RISUG, the male permanent but removable contraceptive without cancer-causing hormones.
Dup of the story I posted hour earlier from the source I believe better describe the whole situation:
Is it the 3rd or 5th then?
Now do cancer next please
Michael Levin is doing that. He's researching morphogenesis, but he also found that cancer is related to that. Basically, all cells communicate with each other with electric potentials to work towards a common goal, like forming an organ or a limb. Cancer happens when that communication is disrupted. It disappears when it's restored.
Just 38.4 million more to go.
Stem cell transplantation is probably not the most effective way to end HIV due to its severe risks and cost: it's much more likely preventative measures like PrEP/PEP and treatments like HAART are much more viable long-term solutions.
Seems to me like every improvement in medical science will be accompanied by a corresponding decrease in individual responsibility. Just like hardware and software.
I've heard young people basically say 'HIV isn't a big deal nowadays so no need to worry'.
Yeah - it's nice not to have to care about and be scared about stuff that is no longer relevant.
This is what technology does.
If HIV were really not a big deal anymore, why should people still worry? If you could have risk-free sex with the seediest of characters, why would it be "not a responsible thing" to do so?
You really should tell your partner if you are infected, on medication or not. You are still dependent on medicine for the rest of your life apart from these cases. So it still is a big deal, but it isn't a death warrant anymore.
Responsibility shouldn't be taught by deadly diseases, you could have said the same about antibiotics.
There's going to be alot of rich people with HIV wanting this.
Poor people, too.
Looks like the hiv resistant donors are more evolved!
> 5th person confirmed to be cured of HIV
40 milions to go :(
That's pretty amazing.
Now do long covid
This is great, but if you have a history of risky behavior or literally having HIV you shouldn't be able to donate blood.
1. You completely missed the point of the article. The (formerly) HIV-positive patient RECEIVED a donation.
2. HIV is already screened for in blood donations. (Whole blood donations also come with a long list of questions which gauge for some things you might consider "risky behavior", like injection drug use or sexual contact with sex workers.)
3. With proper treatment, most HIV patients today have a non-detectable viral load of HIV in their blood. This doesn't mean that they absolutely CANNOT transmit the virus, but that the quantity of virus is vanishingly small. To quote the NIH[0]:
> While it is still possible to transmit HIV to others during [Chronic HIV infection], people who take ART exactly as prescribed and maintain an undetectable viral load have effectively no risk of transmitting HIV to an HIV-negative partner through sex.
[0] https://hivinfo.nih.gov/understanding-hiv/fact-sheets/stages...