Two More Patients HIV-Free After Bone Marrow Transplants | Hacker News Reader

Two More Patients HIV-Free After Bone Marrow Transplants

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I have been part of the United States National Marrow Donor Program

for more than twenty years. Joining the program involves (or used to involve) an initial tissue typing, grouping would-be donors into broad categories of immunologically compatible people. A few years after I joined, when I had moved to another state, I was called up for second-stage testing to see if my antigens were a more specific match for some patient who needed marrow on that occasion. Evidently I was not a close enough match, as I was not asked then to donate marrow. Now my more specific antigen type is on file, and in all the almost two decades since then, I never have any contact with the program except periodic reminders to update the program with my address changes (as I do) and to tell my friends to sign up (as I also do).

http://marrow.org/Join/Join_the_Registry.aspx

What this illustrates is that marrow donations are based on very close antigen matches, and the human leukocyte antigen (HLA) typing used for those matches

http://marrow.org/Patient/Transplant_Process/Search_Process/...

divides humankind into so many small categories that it is difficult for most patients to find a match when they need bone marrow. That, and the considerable expense of harvesting bone marrow from living donors and administering bone marrow to patients in need, keeps marrow donations from being a miracle cure for most diseases. If you join the donor program, as I encourage you to do, you might reach the age of ineligibility for donation (currently age sixty) without ever being called up to donate. That appears to be more likely than not.

A tiny number of cases of a dread disease having patients who "spontaneously" (that is, through mechanisms not fully understood) go into long-term remission from their disease is a routine part of medical practice. AIDS has been scary in the years since it was discovered precisely because of how infrequently patients go into remission, compared to patients with many other dread diseases. Any unusual case of AIDS becoming less grave in its symptoms in any patient is well worth investigating, but it remains to be seen how well understanding those rare cases will generalize to a cure or preventive treatment for AIDS.

The big surprise about AIDS for people like me who were already reading about medical research before AIDS was discovered is how effective antiviral treatments for AIDS have been. The new approach of "treatment as prevention" looks very promising, and there are patients who knew of HIV-positive status in the early 1990s who are still alive and generally healthy--IF they are consistent in taking their antiviral medications--today in 2012, which was not at all expected by researchers even a few years before the protease inhibitor medications were developed. Antiviral drugs are still rare, and AIDS has been a surprising case of effective drug development on a very short time scale.

Thank you for the detailed write-up. I'll definitely consider joining the program!

"Also, the two patients whose cases were presented at the meeting are still taking anti-retroviral medications normally used to treat HIV-positive patients"

How are they trying to detect HIV while at the same time giving the drugs? The drugs make it impossible to find the HIV.

Also note the qualifier: "in their blood cells". HIV reservoirs are not necessarily restricted to blood or blood cell types.

You would expect that these patients need HAART to prevent a reactivating virus from replicating. The Berlin patient is different* because particles generated by a reactivated CCR5-tropic virus cannot infect his new T-lymphocytes.

* though it remains to be seen whether he is truely cured.

You can easily detect HIV in people taking HAART.

That depends on what test you run IIRC.

Could someone in the know explain, given the costs and difficulty of a bone marrow transplant, the likelihood of this becoming a treatment if it does indeed pan out? My initial impression is that it would be very much a "rich Western countries only" solution by a very wide margin.

Yes, definitely this is not a simple treatment. Among other things it requires lifetime immunosuppressive medications.

So at least for now this will never be used in places without a strong medical establishment.

However it's a lot easier to find donations for a cure than for a treatment. So money will probably not be a factor - instead they will have to try to build a complete medical community in each area.

This may end up being a positive thing since good doctors are useful for more than just transplants :)

Places like India will probably have no trouble, but Africa will.

I'm curious - why does the bone marrow transplant require a lifetme mmunorepresants? Is it because otherwise the new immuno-system would attack the host organism?

Also - isn't an organism on immunorepresants essentially n a smilar position as an organism with inactive immun system due to HIV?

Yes, http://en.wikipedia.org/wiki/Graft-versus-host_disease

The drugs do not suppress the entire immune system, just parts of it. (Otherwise the person would die from random infections.)

Thanks :)

This isn't just an issue of wealth. To do a bone marrow transplant you have to find compatible bone marrow, fry your own (very nasty) and then live in isolation (as in an isolated room) till the new marrow kicks in. And that's the best case.

1yr survival rate article: http://www.mskcc.org/blog/msk-s-one-year-survival-rate-after...

Life expectancy alteration: http://jco.ascopubs.org/content/28/6/1011.full (figure 3) (keep in mind the cohort in the study excluded all those dying within 5 years)

would be very much a "rich Western countries only" solution by a very wide margin.

Assuming this method pans out as a cure for AIDS... what starts out today as a solution for those with money causes interest in making it more widely available. Interest leads to new techniques for reducing the cost and complication of bone marrow transplants. Reducing the complication and cost of bone marrow transplants spills over to benefit many other ill people.

Best of all, curing AIDS with any method whatsoever will likely lead to discoveries about the very nature of the disease that could obviate the need for a full marrow transplant.

Arguably more importantly, this gives researchers a very strong new lead on developing therapies that have similar effect to bone marrow transplant.

The thing that makes bone marrow transplantation so expensive (about € 100.000 a pop in Germany, probably more expensive in the US) is that in the time between killing off the patient's own immunosystem and the donor immunosystem taking hold, the patient effectively has no immunosystem at all. This takes about 100 days right now, during which the patient has to be isolated in an environment almost entirely free of pathogens.

So if you want affordable bone marrow transplantation, you either need to find a way to cheaply isolate someone while giving them a very high level of medical care, find a way to grow a complete immunosystem in a few days, or find a new drug that'll effectively fight off every possible infection in a body with no protections of its own. Oh, and then of course you have to affordably stop the donor cells from attacking the host's body, too. Finding a cost-effective drug to cure AIDS looks a lot more likely to me than any of that happening in my lifetime.

It's not just the cost that's the problem, it's the huge risk of a bone marrow transplantation. I've worked in a transplantation ward, and the mortality rates are huge. In our case, about a third of patients was cured following the procedure, a third died within the first few months, and another third developed serious graft versus host disease, a complication where the donor cells attack the host body (5-year-survival-rate 53 % in our patients.)

In patients with leukemia, you usually try at least one round of chemotherapy first, and reserve transplantation for desperate cases where the drugs don't work. Even if this turns out to be viable as a cure for AIDS, I expect it'll work the same way. It's just too deadly as a regular treatment.

once the affordable health-care act goes completely into effect, it may be out of the reach of 99.995% of people in the US too.

My question is that only after 30 years they've discovered the procedure? Was this the first attempt that trying this treatment? What's different now from before if they had?

Such studies are done with patients who need BM transplants for unrelated causes.

These cases are interesting to study because it teaches us what happens when you do reservoir depletion while on HAART. This is a big topic in current HIV research: reactivate integrated HIV to get the host cells killed while blocking viral replication with HAART.

The mortality rate from BMT is extremely high. Much higher than the short term mortality from HIV.

Transplant technology has been around for a while, but only in the past decade have we started to get better at it. This is a function of improved training, improved facilities, experienced doctors, and better post-operation treatment. It had been theorized to work in the past, but only now are we able to implement it. As someone else noted, Bone marrow transplants are among the most difficult transplants.

Could also be a function of triage. AIDS patients may not have been high up the list for bone marrow.

"Treatment" provides a steady income stream, while cure stops all profit.

This is interesting news, large scale transplants do not sound like they would be a viable solution but I wonder how much closer this takes us to applying some sort of gene therapy approach to alter t cell production to mimic the differences produced by this resistant strain of bone marrow.

Imagine how much HIV-Resistant Marrow would be on the open market.

I don't think that's how this works. AFAIU, this works because it literally wipes out your HIV-infected immune system and replaces it with a new one(not HIV-resistant per se). Correct me if i am wrong.

You are correct, I had misread this part:

"While the cells used in Brown’s transplant procedure were specifically chosen from a donor who had a genetic mutation that resisted HIV, these patients received transplants with normal cells."

It sounds like these were simply regular cells.

White blood cell transplant can cure many previous incurable things, including quite a few type of cancer. Too bad you'll have to go to China for the procedure...

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