July 28, 2012
New Stem Cell Transplant Cases Encouraging, but Cure Buzz May be Premature
by Tim Horn
Have two HIV-positive stem cell transplant patients been cured of their infection? Several mainstream media headlines following a presentation by Boston researchers on Thursday, July 26, at the XIX International AIDS Conference (AIDS 2012) suggest they have. But while the case reports are intriguing and encouraging—both patients have undetectable blood- and cell-based virus and have been experiencing reductions in their HIV antibody levels following chemotherapy, stem cell transplants and while remaining on antiretroviral therapy following cancer diagnoses—references to a cure may be premature ("Two More Patients HIV-Free After Bone Marrow Transplants" reads an ABC News headline).
The latest case reports were reported by Timothy Henrich, MD, an infectious disease physician at Brigham and Women’s Hospital in Boston and his colleagues. He began by referencing the familiar case of Timothy Brown, colloquially known as the “Berlin Patient,” who was cured of his leukemia and HIV infection following high-dose chemotherapy and a stem cell transplant from a donor whose CD4 cells lacked the CCR5 receptor needed by HIV to establish infection.
Scientists hope to duplicate Brown’s outcome in other patients—notably those with certain cancers who require grueling stem cell transplants to save their lives—using CCR5-deficient stem cells from adult donors, cord blood samples and gene modification strategies (using zinc finger nucleases, for example).
Questions, however, still remain surrounding Brown’s case, notably: To what extent did his pre-transplant chemotherapy contribute to the destruction of the reservoirs of HIV in his body? Does graft-versus-host disease—the targeting of donors’ foreign immune system cells by transplant patients’ own cells—aid in eradicating reproducible virus?
Henrich’s team, in turn, wanted to explore the long-term effects of pre-conditioning chemotherapy and stem cell transplants in patients who didn’t receive cells from donors with HIV-susceptible cells. They focused on two Brigham and Williams patients who were living with HIV and underwent transplants for lymphoma-related cancers. But unlike Brown, they received transplants using cells expected to produce CD4s carrying the CCR5 receptor; they also received less-intensive chemotherapeutic pre-conditioning than Brown, so that they could remain on their antiretrovirals during and after the transplant process.
Both patients remained on ARVs while undergoing transplants—one was receiving Atripla (efavirenz/tenofovir/emtricitabine) the other was receiving Isentress (raltegravir) plus Truvada (tenofovir plus entrictabine)—and both were treated with immune-suppressive drugs following their transplants after experiencing grant-versus-host disease.
Looking back at blood samples collected from the patients during post-transplant follow up—one patient had roughly two years of samples available; the second had roughly three-and-a-half years of follow-up samples available—Henrich and his colleagues made a number of encouraging discoveries.
Using highly sensitive viral load technology, levels of replication-competent HIV—if it is still present—eventually became too low to be accurately measured, compared with what is typically seen in people receiving antiretroviral treatment ((less than a half copy per milliliter of blood plasma versus 1 to 2 copies per milliliter of blood plasma, respectively).
As for HIV-DNA inside cells in blood samples, Henrich and his group noted that genetic material was detected in the months following stem cell transplantation. But by day 200 in one patient and day 300 in the other, HIV-DNA became undetectable. In fact, efforts to “grow out” the virus in samples from the patients at day 1,266 and 652, respectively, proved fruitless.
While HIV antibodies are still detectable in both patients, substantial decreases in antibody levels began approximately 200 days following their transplants.
Are these patients cured of their HIV infection? While Henrich suggested the data are encouraging, noting the “substantial and sustained reduction in the HIV reservoir” and that the “declining HIV-specific antibody levels provide further evidence for minimal persistence of HIV antigen” are important findings, some key pieces of the puzzle are still missing.
Unlike Brown, who has remained off HIV treatment for more than five years and has produced tissue samples devoid of replication-competent HIV, the two patients under Henrich’s care have yet to initiate an antiretroviral treatment interruption and do not yet have tissue samples available. These are necessary, Henrich explained, “to fully assess the extent of HIV reservoir reduction after stem cell transplantation.”
“We’re being very careful to refer to our patients as not being functionally cured,” added Daniel Kuritzes, MD, a Harvard Medical School researcher who has been working alongside Henrich.
Search: hiv, cure, stem cell transplant, hsct, boston, brigham and williams, henrich, reservoirs, graft-versus-host, gvhd, antiretrovirals, treatment, eradication, aids 2012
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comments 1 - 15 (of 20 total) next
Benny, Beacon, 2013-02-14 12:05:07
crystalclear, , 2013-01-10 09:11:23
A cure is not in the financial interest of pharma and their stakeholders. Do not expect a cure from any research funded by the US government. Our only hope is India or China.
NY Ngubane, RSA,KZN,Durban, 2012-12-12 09:18:21
I am HIV positive...I would be very happy to be the first South African agree for volunteer for a New stem transplant. Please I am so desparate.
Jarlath Healy, Jonestown, TX, 2012-08-24 02:26:49
I'm in the early stages of completing my Microbiology degree. I switched majors because I watched a video of a fifteen year old kid who was born with HIV. If I had only one cure, I'd give it to him. We all need reinsurance and hope for a cure. If it's not found before I graduate. It's the first thing I plan to be researching in.
keith, EU, 2012-08-06 18:21:51
I still reckon we could have A cure if not THE cure by AIDS 2014.
I read a story last week (can't find the link) that mentioned a case from the early 90's of a HIV+ man who got a BMT. He died a year later but in his autopsy there was no sign of HIV
There are Cord blood tests going on in europe and US if they work as I said before there is a cure. We will know soon
They also seem confident of setting a preventative vaccine in the next 10 years new tests are planed for S.A and Thialand
Annon, Hollywood, 2012-08-06 13:26:38
I just want to be cured n have my life back! If this works...... It would mean getting my LIFE back!
Tim Horn, AIDSmeds, New York, NY, 2012-08-06 10:23:30
MineMan, shooting the messengers is pointless. No new zinc finger nuclease (ZFN) clinical research, either from Sangamo or other groups, was presented at AIDS 2012. As for the two clinical trials you reference, I made a point of mentioning these (with hyperlinks) in my July 20 summary of the Towards an HIV Cure symposia.
MineMan, , 2012-08-06 09:23:25
I find it very strange that none of those covering the IAS meeting in DC mention the research and clinical trials that Sangamo Biosciences is doing. 2 PH II trials that were at CROI touted as a "functional cure", Several presentations by scientists and persons participating in the trials were passed over as non-events. When they may have been the most important of the meeting.
Very dissapointed in the coverage.
Don, Asheville, 2012-08-02 16:57:36
This is exciting news. I hope more becomes of this method. Just imagine the ramifications if it proved to be a sucessful way to rid the body of the virus!
I realize it's premature, but exciting just the same.
Diego, , 2012-08-01 20:07:36
I think i'm understanding how this is working and why it is. It seems as time progresses the infection everywhere in the body decreases within time. I believe this treatment completely interrupts and knocks the main cell out of place then the 32 cell then destroys that and destroys bad cells overtime. Its been sounding like HIV/AIDs was a cancer all along.
keith, , 2012-07-31 19:13:03
Interesting TV i/v with Brown and someone from AMfar
What's very interesting in mention mention of cord blood and more info "coming soon" from Europe.
I believe this could work and maybe should be used in patients were drugs no longer work.
BREALNYC, New York, 2012-07-31 11:03:44
Any good news is good news. Yet, having a cure only matters when it's available to YOU.
Keith, , 2012-07-31 10:20:56
I am not saying BMT is the only answer and if these two men are cured then that is it.
But if it has worked then HIV is curable with BMT.
How long will the tests you mention take are there human trials happening or planed.
Ranjan, , 2012-07-31 09:51:57
Surprisingly there is no further news about the Canadian vaccine trials commenced on humans in Jan 12 with the approval of FDA. One of the largest gatherings for cure ofor HIV is going on and the expectation was so high. All we hear is only new course and effort to find a cure and nothing about some trials which commenced a few years back. Even the breakthrough by Israeli scientists of some peptide based cure announced in Sept 2010 but no further news. Its quite dissapointing to say the least
Joseph Charles Butler, Oakland/Lake Merritt, 2012-07-31 00:32:11
comments 1 - 15 (of 20 total) next
I argue the fact you have to take out the immune system completely to then perform the curable action and then put the immune system back in. I am with a research study with University California San Diego called The Edge that focuses on HIV NeuroBehavioral Research and I think there is another way such as turning it into a pill format or maybe into a shot in the butt type of cure. Just need more time, analizying, and patience.
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