5th person confirmed to be cured of HIV
abcnews.go.com
abcnews.go.com
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.)
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.
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.)
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.
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)
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.
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.
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.
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.
> 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?
This is an outdated and objectively incorrect description of HAART.
> but dismissing the heavy questions of a persons life with "basically normal" is not helpful.
"Basically normal" is an approximately correct description of the life of most HIV+ people who have easy access to HAART. What's not helpful is responding to that with fearmongering based on incorrect and/or grossly outdated information.
There's a difference between fearmongering and informed consent, and I would ask you to refrain both from spreading misinformation and from making personal attacks. Accusing someone of "fearmongering" for pointing out risks you falsely say do not exist is inappropriate.
Your comment literally claims that long-term HAART carries a significant (or even certain) risk of long-term liver damage, a claim which is baseless and unsupported.
You're also conflating acute adverse reactions - which are astronomically rare - with long-term side-effects, when there's no relationship between the two.
Not only are tenofovir and emtricitabine safe for the liver, but they are literally commonly prescribed for people who have chronic liver problems because they are so well tolerated. People who can't take Tylenol are able to take them. It's a gross mischaracterization to suggest that they cause "decades of liver damage", a claim which is soundly contradicted by medical literature.
> There's a difference between fearmongering and informed consent, and I would ask you to refrain both from spreading misinformation and from making personal attacks.
I never made any personal attack at any point.
I would, however, flip this request back at you and ask you to stop spreading misinformation, which is what you are clearly doing.
> Your insistence on gaslighting does not lend credibility to your other claims.
Your comparison to Tylenol is misleading. People aren't required to receive regular liver enzyme tests before being allowed to use Tylenol.
Read the guidelines yourself. Accusing people of fearmongering is a personal attack. If you think I'm wrong (and the FDA is wrong) about the risk of liver damage, feel free to present that evidence here (or better yet, to the FDA, so people can have better access to PrEP). Don't make false and ad hominem claims about my motivations.
People aren't required to receive "regular liver enzyme tests" before taking these drugs either.
> free to present that evidence here
You've made a lot of claims without presenting any evidence to back any of them up. Moreover, your claims could be trivially debunked by even a cursory search. The burden is not on me or others to do that work when you yourself present zero evidence for any of the fantastical claims you make.
> Don't make false and ad hominem claims about my motivations.
I never made any claim about your motivation. "Fearmongering" is a specific, descriptive term about your actions, the effect they have on others, and their factual basis (or lack thereof).
On the other hand, you accused me of gaslighting (before editing it out of your comment and replacing it with a different accusation). That is an ad hominem attack, ascribing specific and malicious motivations.
Also: https://dictionary.cambridge.org/us/dictionary/english/fearm...
It's an ad hominem.
Incorrect. A one-time test of liver function was previously sometimes suggested before starting PrEP specifically... but not for the reason you think. And it was never required.
Ongoing liver enzyme tests are neither required nor recommended. In fact, Truvada and Descovy were shown to be so safe during clinical trials that routine liver function tests are explicitly contraindicated for patients with no other comorbidities.
> It's an ad hominem.
Even if I were accusing you of intentionally spreading fear and misinformation, that still would not be an ad hominem: https://en.wikipedia.org/wiki/Ad_hominem
You are correct. I was mistaken.
> Even if I were accusing you of intentionally spreading fear and misinformation
You were. That's what the word means.
> that still would not be an ad hominem
It would not constitute an ad hominem fallacy. It is still an ad hominem attack and is still deeply unproductive.
From 2011 to 2016, overall life expectancy at 21 years of age for individuals with HIV infection who initiated ART at a CD4 cell count of 500/μL or greater was 57.4 years (95% CI, 55.7-59.1 years) and for uninfected adults was 64.2 years (95% CI, 64.0-64.4 years), corresponding to a difference of 6.8 years (95% CI, 5.0-8.5 years)
According to whom? Who gets to make the choice between 57 years of drugs and stigma versus 64 years of being cured?
Based on their 2010 alloHCT volume, centers were categorized as low-volume (≤40 alloHCTs; N=42 centers, 1,900 recipients) or high-volume (>40 alloHCTs; N=41 centers, 9,637 recipients). 100-day survival was 86% (95% CI, 85–87%) in high-volume compared to 83% (95% CI, 81–85%) in low-volume centers (difference 3%; P<0.001). One-year survival was 62% (95% CI, 61–63%) and 56% (95% CI, 54–58%), respectively (difference 6%; P < 0.001).
Not to mention that the "64 years" comparison is not the correct reference point here, because it's talking about people who were never infected with HIV in the first place, not people who have received a stem cell transplant.
The stem cell transplant almost certainly reduces both your lifespan and QALS in the long term, not just the first two years. Yes, it might be worth it if you have cancer, but it's not like it suddenly makes you clinically equivalent to a person who has never had HIV!
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)
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
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.
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:
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.
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.
> 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!
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.
I suggest watching the movie 'Gattaca' ;-)
Seriously though, it is really good
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.
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.
I've heard young people basically say 'HIV isn't a big deal nowadays so no need to worry'.
For example, there is a distinction between low risk activity such as oral sex and higher risk activity such as anal. The latter will often involve a brief discussion of risk: condom use, PrEP, status, so that both participants are on the same page.
Note that the treatment in this article, as others have pointed out, is really not that. This is an extremely violent treatment that no one in their right mind would use for HIV - it's just a last-resort treatment for fatal blood cancers that happened to have cured HIV in some patients.
Responsibility shouldn't be taught by deadly diseases, you could have said the same about antibiotics.
40 milions to go :(
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...