(London,Berlin,Dusseldorf, etc) Stem Cell HIV remission cases.

[geobee]

This is a stem-cell Delta-32 experiment (aka Tim Brown).  Here's the juicy part (I always take my juice with a grain of salt!)

Scientists from the Institute for AIDS Research IrsiCaixa in Barcelona and the Gregorio Maranon Hospital in Madrid have managed to remove the virus from the blood and tissues of six patients using the treatment.

But the research, published on Monday in the Journal of Internal Medicine, said one patient now has no antibodies fighting the infection, suggesting it has been completely eliminated.

Here's the article -- it's short:

http://www.theolivepress.es/spain-news/2018/10/16/spanish-doctors-eliminate-hiv-from-patient-in-stem-cell-transplant-trial/

[Jim Allen]

Well time will tell with this one, we all recall the kids who were "cured" but when testing a few years later it was back. Long term remission perhaps

The patients are keeping up their antiretroviral treatment,

Currently the Berlin patient has a functional cure but even than he still has HIV in some tissues just not replicating or its in a dormet state in laymens terms.

Always something to learn though

Jim

[geobee]

I thought it was interesting that the one patient had no anti-bodies at all.  If he goes for several years without anti-bodies -- well, that would be something.  Sign me up! 

[I *did* try to sign up a few years ago for a Sangamo D32 trial.  They couldn't get enough HIV out of my blood to do a genotype and I was DQ'd]

[Jim Allen]

Even the Berlin patient had a few negative Elisa results if i recall for a while, anyhow i suspect it will be more a possible functional cure one day for some, with longer treatment gaps if it works out, we will see how time goes on. In the meantime it will be interesting to see the published results from this latest phase.

Jim

[Jim Allen]

Here is an abstract BTW and ill fish out the full one later this week.

http://annals.org/aim/article-abstract/2707334/mechanisms-contribute-profound-reduction-hiv-1-reservoir-after-allogeneic-stem

Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant

Abstract
Background:
The multifactorial mechanisms associated with radical reductions in HIV-1 reservoirs after allogeneic hematopoietic stem cell transplant (allo-HSCT), including a case of HIV cure, are not fully understood.

Objective:
To investigate the mechanism of HIV-1 eradication associated with allo-HSCT.

Design:
Nested case series within the IciStem observational cohort.

Setting:
Multicenter European study.

Participants:
6 HIV-infected, antiretroviral-treated participants who survived more than 2 years after allo-HSCT with CCR5 wild-type donor cells.

Measurements:
HIV DNA analysis, HIV RNA analysis, and quantitative viral outgrowth assay were performed in blood, and HIV DNA was also measured in lymph nodes, ilea, bone marrow, and cerebrospinal fluid. A humanized mouse model was used for in vivo detection of the replication-competent blood cell reservoir. HIV-specific antibodies were measured in plasma.

Results:
Analysis of the viral reservoir showed that 5 of 6 participants had full donor chimera in T cells within the first year after transplant, undetectable proviral HIV DNA in blood and tissue, and undetectable replication-competent virus (<0.006 infectious unit per million cells). The only participant with detectable virus received cord blood stem cells with an antithymocyte globulin–containing conditioning regimen, did not develop graft-versus-host disease, and had delayed complete standard chimerism in T cells (18 months) with mixed ultrasensitive chimera. Adoptive transfer of peripheral CD4+ T cells to immunosuppressed mice resulted in no viral rebound. HIV antibody levels decreased over time, with 1 case of seroreversion.

Limitation:
Few participants.

Conclusion:
Allo-HSCT resulted in a profound long-term reduction in the HIV reservoir. Such factors as stem cell source, conditioning, and a possible “graft-versus-HIV-reservoir” effect may have contributed. Understanding the mechanisms involved in HIV eradication after allo-HSCT can enable design of new curative strategies.

Primary Funding Source:
The Foundation for AIDS Research (amFAR).

[Ptrk3]

From the October 17, 2018, edition of POZ, another story on the subject of this thread:

https://www.poz.com/article/search-repeat-berlin-patient-hiv-cure-questions-worked

More detail from the October 15, 2018, edition of MedPage Today:

https://www.medpagetoday.com/hivaids/hivaids/75717?xid=nl_mpt_DHE_2018-10-16&eun=g605133d0r&pos=&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202018-10-16&utm_term=Daily%20Headlines%20-%20Active%20User%20-%20180%20days

[Cosmicdancer]

Is there more information about the 6 people who underwent the stem cell transplant?  Were they people who had some type of cancer or leukemia? They say they studied 6 people who had survived 2 years after treatment, did some people die? Did they give them chemo to wipe out their existing immune system? How arduous was the transplant process, and what side effects did they experience? 

Okay, after posting this I noticed the link to the Poz article which addressed most of my questions.

I look forward to reading more articles about this.

[CaveyUK]

maybe it's just me, but if a possibility to send HIV into 'remission' involves non-routine, high-risk highly invasive surgical procedures, I think I'd prefer to just stick with my pill-a-day...

[Gladragsguy]

And we won't even mention the prohibitively astronomical cost of this type of treatment, or that finding the right donor is extremely difficult, or the idea that you could possibly do more damage to yourself than when you started out, or that you might have to be on even more expensive anti-rejection medications possibly for the rest of your life?  All of this for a chance to remove the Scarlet H? Power to the researchers because research like this might help us to find the cure...but this is not it...just research into the mechanism. Fight stigma that's the real cure.

[fabio]

I,too, believe that if this procedure were to happen,the risks would be many. Getting "cured" is nice and all,but having a functioning life is the ideal and the arvs are giving us that.

[Prince_Bernhard]

Exciting news from the CROI Conference:

H.I.V. Is Reported Cured in a Second Patient, a Milestone in the Global AIDS Epidemic

Scientists have long tried to duplicate the procedure that led to the first long-term remission 12 years ago. With the so-called London patient, they seem to have succeeded.

For just the second time since the global epidemic began, a patient appears to have been cured of infection with H.I.V., the virus that causes AIDS.

The news comes nearly 12 years to the day after the first patient known to be cured, a feat that researchers have long tried, and failed, to duplicate. The surprise success now confirms that a cure for H.I.V. infection is possible, if difficult, researchers said.

The investigators are to publish their report on Tuesday in the journal Nature and to present some of the details at the Conference on Retroviruses and Opportunistic Infections in Seattle.

Read more: https://www.nytimes.com/2019/03/04/health/aids-cure-london-patient.html

[Jim Allen]

18 months without rebounding is interesting, the way its done is interesting and provides insights into new idea's. Although its far from any workable or scalable treatment plan, more the exceptions that confirm the rule.

Jim

[virgo313]

Just read this news. London patient.
Possible another person cured?
https://www.nytimes.com/2019/03/04/health/aids-cure-london-patient.amp.html

[terrymoore]

Have you heard of this?

https://www.bangkokpost.com/news/world/1639538/london-patient-second-case-ever-of-hiv-remission#cxrecs_s

[Jim Allen]

So the October report covered 6 patients undergoing this, and explained the process.

My understanding is this the same, its IciStem patients being tracked across the EU undergoing the same, some (most) post treatment for cancer, the London Patient is number 36 and there is also a 2nd patient from all this showing some promise for a long term remission.

My own thoughts are 18 months without rebounding is very interesting, also the way its done is interesting and, it provides insights into new idea's. Although its far from any workable or scalable treatment plan, more the exceptions that confirm the rule.

Jim

[leatherman]

I like that this thread title uses the most correct word "eliminate" rather than the very misleading "cure"

unlike the Berlin patient and this London patient who have had good results, this news forgets to mention the dozen or so other patients who have tried this procedure and have died from their cancer or this procedure.

It's an extreme procedure done on PLWH who also have cancer (usually leukemia) as basically a last chance effort. The patient's immune system is killed off by radiation/chemo, stem cells are transplanted (if there is a matching donor), and anti-rejection meds are taken. Hopefully a patient can survive the procedure (which itself has only a 62% survival rate), hopefully the cancer is cured or goes into remission, and then the patient struggles to hopefully recover their health.

[Jim Allen]

That and, i'm not saying this to step on anyone's excitement as I do get it. I am living with this as well, like the rest of us.

However its not a new procedure, yeah its been tweaked but its not going to be a "cure" anytime soon in the sense of the population living with HIV. The noted exception being the odd few, and its great for the person(s) themselves.

Looking at the bigger picture however I would agree with the National-AIDS-Trust tweet, still too many people dying each year a small million and, there are other treatment improvements to focus & invest in.


https://twitter.com/NAT_AIDS_Trust/status/1102878067343704064


P.S Does remain interesting news of course and, a topic to discuss  

[geobee]

Interesting item from the article re: half of us have X4 virus so the bone marrow transplant wouldn't make any difference.  Still, it's cool that there's a second guy.  Glad for him!

[fabio]

It made international news,apparently. I now realised it's a bone marrow transplant. Didn't the Berlin patient do the same? Also if I remember right it's a risky procedure.
At least he made it.....

[Jim Allen]

Yeah, similar indeed

[fabio]

My brothers friend had a bone marrow transplant,he had leukaemia. The first three months seemed ok for him,yet my brother told me that the cells rejected his body or something like that (I don't remember exactly). So after that he went on a coma and in the end died.
I also hate the way they say "cure" in the news,just to glorify something. Journalism at its worst.....

[Loa111]

I'm sure most of you saw this today on the news...
UK patient 'free' of HIV after stem cell treatment.
https://www.bbc.com/news/health-47421855

[Jim Allen]

Here is the early release publication (Free Abstract)

HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation
https://www.nature.com/articles/s41586-019-1027-4

POZ.com
A 2nd Man’s HIV Is in Long-Term Remission, but Is He Cured?
In full: https://www.poz.com/article/2nd-mans-hiv-longterm-remission-cured

In short:

In 2013, excitement shot around the globe when researchers suggested a baby in Mississippi had been functionally cured of HIV after clinicians started her on an atypically aggressive ARV regimen soon after birth. While an initial case report found no evidence of replicating virus in the child after she spent months off ARVs, she ultimately experienced a viral rebound 27 months after she was taken off HIV treatment.

In the years since that particular disappointment, researchers have become more measured about the language they use when referring to outcomes in the effort to cure HIV. Many investigators in the field prefer terms such as “viral remission” or “posttreatment control of HIV” as the ultimate goal of such research. Familiar from cancer treatment, the term “remission” acknowledges at least the outside possibility of a return of the virus.

Scientists, however, are so certain that Brown’s virus is gone that they have asserted he is indeed cured of HIV.

Both Brown and the London Patient received stem cell transplants with immune cells from donors drawn from an international registry who lacked the gene that expresses the CCR5 coreceptor on the surface of CD4 cells. Most HIV attaches to that coreceptor in order to begin the process of infecting cells. (Such HIV is known as CCR5-tropic virus to distinguish it from CXCR4-tropic virus, which attaches to the coreceptor on the surface of CD4s of that name.) The technical term for the donor’s genetic profile is that he or she is homozygous for the CCR5-delta32 mutation. This genetic abnormality tends to occur among about 1 percent of those of Northern European ancestry.

Brown now takes Truvada (tenofovirdisoproxilfumarate/emtricitabine) as pre-exposure prophylaxis (PrEP) to ensure he does not contract HIV. The London patient has received counseling regarding use of PrEP, but at this time has opted not to take it.

The case of the London Patient is remarkable given that it follows years of concerted efforts on the part of researchers to replicate the success seen with Brown with similar strategies. (Brown’s case was first reported in 2007.) There have been numerous reports of failures to prompt extended viral remission in people with HIV using stem cell transplant methods.

There are, in fact, a handful of people around the world outside of the London Patient who are in a state of years-long viral remission after beginning ARV treatment early in the course of their infection and later interrupting their HIV regimen. These include the members of the VISCONTI cohort, a young French woman and an African child.

Promisingly, the British man received a much more tolerable treatment to condition him for his stem cell transplant compared with the brutal conditioning that Brown endured prior to the two transplants he had to receive to beat his own case of acute myeloid leukemia. Brown nearly died from his cancer treatment.

Note that in both cases the men received highly toxic treatments that would be appropriate only for individuals facing potentially fatal cases of cancer. It would not be ethical to put other people with HIV through a comparable treatment if they did not similarly have cancer.

[Mightysure]

I thought it was interesting that the one patient had no anti-bodies at all.  If he goes for several years without anti-bodies -- well, that would be something.  Sign me up! 

[I *did* try to sign up a few years ago for a Sangamo D32 trial.  They couldn't get enough HIV out of my blood to do a genotype and I was DQ'd]

Really? I was DQD from a Vorinostat trial becsuse they couldn't find enough viral DNA to quantify the affects of thr study drug.  Why don't they get people like us to do a cure study for?

[Ptrk3]

Another one?

From the March 5, 2019, edition of New Scientist:

(Lede paragaph):  Following news of a man in the UK who has been free of HIV since his cancer treatment, a similar case has been reported by researchers who treated a patient in Germany. Together, they add to evidence that it may be possible to cure HIV.

Link to story:

https://www.newscientist.com/article/2195780-a-third-person-may-have-become-hiv-free-after-a-bone-marrow-transplant/

[Jim Allen]

Yeah, the 3rd one is  “the Düsseldorf Patient” however he's only been off meds for 4 months so too early to tell, as he could still experience viral rebound.

That also goes for the London patient, although at 18 months he seems to be going the distance. The October 2018 press release indicated 6 people had survived 2 years post treatment, and that 5 had undetectable VL so I suspect over the months/years ahead we might hear about 1 or 2 more people from this going off the meds with remission.   

The British man is actually one of 38 HIV-positive individuals who have received stem cell transplants (this includes six people whose donors did not have the CCR5 mutation) that researchers hope will lead to long-term remission of the virus among them. Another study presented at CROI concerns one of these individuals, referred to as “the Düsseldorf Patient,” who has been off ARVs for four months without a viral rebound.

“[At] 18 months posttreatment interruption it is premature to conclude that this patient has been cured,” the study authors concluded about the London Patient in the Nature paper.

https://www.poz.com/article/2nd-mans-hiv-longterm-remission-cured

[geobee]

I'm having real problem with the ethics of this.  This "cure" is pretty dangerous and expensive and will never be widely available and ... yet... I secretly wish I could give it a shot. 

[MadDog125]

Has anyone heard of the "Brittish paitient".  It seems the Berlin paitient may not have been a fluke.  From what the bio magos types have said it's not the answer (risks of bone marrow transplants, 50% viability for blood cell mutation cited). 

Still though it's hard not to get excited.  It may only be a second paitient and a possible fluke, but it proves at least the possibility.  Anyone else see this as a happy thought?

[joemutt]

https://www.youtube.com/watch?v=o0hduPJJ9ng

[Jim Allen]

Enjoyed reading this opinion piece in the NY Times, so sharing it. I agree with him on it being a distraction of sorts
 
In full:
https://www.nytimes.com/2019/03/09/opinion/sunday/cure-hiv-aids.html

In short:

This is Not A Cure for My H.I.V.

The news about a second person who may be free of the infection is a distraction from the work we need to keep focusing on.

By Gregg Gonsalves
Mr. Gonsalves is a longtime AIDS activist and a researcher.

H.I.V. is not going away anytime soon. I’ve been living with it for more than 20 years and have seen the overhyped stories promising a cure around the corner pop up regularly, particularly around the time of big AIDS conferences. The news last week that a second person seems to have gone into long-term remission from H.I.V. after a stem cell transplant is a real scientific advance. But I fear the sensationalism with which this report was received could do more harm than good. It obscures the actual struggles we face in combating this epidemic.

In this most recent case, cancer was an opportunity that offered the chance to cure two diseases at once. The individual, known as the “London patient,” received the transplant from a donor with a genetic mutation that conferred resistance to the H.I.V. infection. He was the second person ever to sustain long-term viral suppression in the absence of antiretroviral treatment. Timothy Ray Brown, also known as the “Berlin patient,” underwent a similar procedure 12 years ago, with the same remarkable results.

But stem-cell transplants from these rare donors are unlikely to be used for the average H.I.V.-positive patient without cancer, because of the risks involved and the impracticality and costs of these procedures. In reality, a cure for H.I.V. remains a distant dream and the focus on the two “cured” patients is a distraction from the work that we still have to do, that’s more pragmatic and not as high-profile as news that someone is possibly free of the infection.

[Jim Allen]

I know there have been a few interviews etc with Castillejo, this update relates more to the treatment details and follow-ups though.

https://www.poz.com/article/famed-london-man-probably-cured-hiv

Famed London Man “Probably” Cured of HIV

Gupta told POZ that he considered Castillejo in a state of long-term remission from HIV and that it was highly likely that the man is indeed cured.

[Jim Allen]

A woman in the USA has been in remission for 14 months without ART after a stell cell transplant with the CCR5 delta-32 mutation.  I've added links at the end of this post, including the initial 2018 publication of this case.

i-base full write-up:
https://i-base.info/htb/42182

In Short:

The case involves a woman living with HIV who was diagnosed with acute myelogenous leukemia (AML), a life-threatening cancer, in 2017. The researchers sourced cord blood stem cells from a donor homozygous for the CCR5 delta-32 mutation that prevents expression of the CCR5 co-receptor that most HIV strains use as an entryway into cells.

The aim was to treat the cancer while also generating a new immune system made up of HIV-resistant cells, following the model that has produced three other known cases of likely HIV cures in men (Timothy Ray Brown, Adam Castillejo and the Düsseldorf patient).

A difference with prior cases is that stem cells from umbilical cord blood are less efficient at generating a new immune system after transplantation, so the woman also received stem cells from the peripheral blood of an adult relative who lacked the CCR5 delta-32 mutation.

HIV-1 remission IMPAACT P1107
https://ww2.aievolution.com/cro2201/index.cfm?do=abs.viewAbs&abs=3310

The 2018 publication of this case:
https://www.sciencedirect.com/science/article/pii/S0006497119382333

There is also a thread on the London, Berlin and Dusseldorf patients.
https://forums.poz.com/index.php?topic=70974.msg755934#msg755934

[Da2020]

This is excellent news. They have also mentioned that they could potentially scale this up to 50 people/year. Still not there yet, but good news reagrdless

[Jim Allen]

Hope the man is able to remain in HIV remission.

https://www.poz.com/article/another-man-appears-cured-hiv-stem-cell-transplant

While the risky procedure is not suitable for most people living with HIV, it offers clues for more feasible approaches.

The City of Hope Patient received a stem cell transplant for cancer treatment using cells from a donor with a rare genetic mutation, called CCR5-delta32, that blocks HIV from entering T-cells. He has remained free of HIV for more than 17 months after stopping antiretroviral therapy.

So far, only a handful of people have been cured of HIV after stem cell transplants. The first, Timothy Ray Brown (known as the Berlin Patient) received two transplants to treat leukemia in 2006. His doctor, Gero Hütter, MD, came up with the idea to use cells from a donor with the CCR5-delta32 mutation, speculating that it might cure both cancer and HIV.

Brown stopped antiretroviral treatment at the time of his first transplant, but his viral load did not rebound. Researchers extensively tested his blood, gut and other tissues, finding no evidence of functional HIV anywhere in his body. At the time of his death in September 2020, due to a recurrence of leukemia, he had been free of HIV for more than 13 years.

The second man, Adam Castillejo, known as the London Patient (featured in POZ’s June 2022 issue), underwent a stem cell transplant to treat lymphoma, receiving cells from a donor with the same mutation. A year and a half after the transplant, with no evidence of viable HIV, he stopped antiretroviral therapy in September 2017. He has now been HIV-free for more than four years.

[leatherman]

‘Eliminate’

Thank you for being better than poz.com by using the correct term.


Now to fend off the family and friends, with so much hope for me in their voices, who'll send me a link to this "amazing" news wondering when I'll be able to get this cure. ugh.

[Jim Allen]

Now to fend off the family and friends, with so much hope for me in their voices, who'll send me a link to this "amazing" news wondering when I'll be able to get this cure. ugh.

Every time some over-enthusiastic company mentions the word "cure" in a press release to gain attention and funding, or the media run stupid headlines on some petri dish, I spend the afternoon having to explain why I'm not nor are the other 37.7 million going to be "cured" anytime soon to my friends & family.

[Da2020]

There was also another woman who has been off ART for 15 years, considered to be a post treatment controller. Her case was also presented at the same conference

[Jim Allen]

See, the Düsseldorf patient is trending in some Dutch news outlets today. Nothing new, just that the patient remains in HIV remission at the four-year mark.

https://www.parool.nl/nederland/umc-utrecht-derde-europeaan-met-hiv-officieel-genezen~b24b02cc/.

[Jim Allen]

See, the Düsseldorf patient is trending in some Dutch news outlets today. Nothing new, just that the patient remains in HIV remission at the four-year mark.

https://www.parool.nl/nederland/umc-utrecht-derde-europeaan-met-hiv-officieel-genezen~b24b02cc/.

English article on POZ.com https://www.poz.com/article/german-man-free-hiv-nearly-10-years-stem-cell-transplant

[Jim Allen]

A woman in the USA has been in remission for 14 months without ART after a stell cell transplant with the CCR5 delta-32 mutation.  I've added links at the end of this post, including the initial 2018 publication of this case.

i-base full write-up:
https://i-base.info/htb/42182

In Short:

HIV-1 remission IMPAACT P1107
https://ww2.aievolution.com/cro2201/index.cfm?do=abs.viewAbs&abs=3310

The 2018 publication of this case:
https://www.sciencedirect.com/science/article/pii/S0006497119382333

I see this case trending in the media. There is no update, although the full paper has been published, and it's an interesting read.

HIV-1 remission and possible cure in a woman after haplo-cord blood transplant
https://www.cell.com/cell/fulltext/S0092-8674(23)00173-3

[Jim Allen]

I see this case trending in the media. There is no update, although the full paper has been published, and it's an interesting read.

HIV-1 remission and possible cure in a woman after haplo-cord blood transplant
https://www.cell.com/cell/fulltext/S0092-8674(23)00173-3

POZ.com article on this case: https://www.poz.com/article/mixedrace-woman-potentially-cured-hiv-using-stem-cell-transplant

[Jim Allen]

Geneva case - HIV remission at 20 months after stem cell transplant for cancer treatment. Early days and continued monitoring, and further testing is needed.

POZ.com article: https://www.poz.com/article/geneva-man-may-cured-hiv-wildtype-stem-cell-transplant

In Short:

Known only as the Geneva Patient, a sixth person appears to have been cured of HIV after a stem cell transplant for cancer treatment, according to a case study presented at the International AIDS Society Conference on HIV Science (#IAS2023) in Brisbane, Australia.

The man received a transplant in July 2018 using so-called wild-type stem cells without the CCR5-delta32 mutation. He stopped antiretroviral treatment in November 2021 and has no evidence of HIV rebound or replicating virus 20 months later, Asier Sáez‐Cirión, PhD, of Institut Pasteur in Paris, and Alexandra Calmy, MD, PhD, of Geneva University Hospitals, reported at a preconference press briefing.

“All the immunological markers we have analyzed have been unable to detect HIV products,” Sáez‐Cirión said. “We cannot exclude that there is still some virus present…so there may be viral rebound in the future, although we hope this situation of viral remission remains permanent.”