December 10, 2010

Berlin Patient Follow-Up 'Strongly Suggests' HIV Cure

Editor's note: Soon after this article was posted to AIDSmeds and POZ, the editorial staff discovered that the long-anonymous Berlin Patient has decided to come forward, for the first time ever, in a profile published in the December 9 issue of Stern magazine. He is 44-year-old Timothy Ray Brown. (Click here for an approximate English translation of the profile teaser posted to stern.de.)

The “Berlin Patient”—a man living with HIV who underwent a transplant involving HIV-resistant stem cells in 2007 for the treatment of leukemia—has been classified as cured of his HIV, according to an update of the patient’s experience published online, ahead of print, on December 8 by the journal Blood. The man has remained off HIV treatment for three-and-a-half years with normal CD4 counts and no evidence of HIV replication.

Though it was initially suspected that HIV archived in the man’s cells would begin proliferating once his immune system began to recover from pre- and post-transplantation treatment, this was not observed and the team monitoring the patient now conclude, “our results strongly suggest that cure of HIV has been achieved in this patient.”

The intriguing case, first reported at 15th Conference on Retroviruses and Opportunistic Infections (CROI) in 2008, involved a 40-year-old American HIV-positive man living in Berlin with a relapse of acute myeloid leukemia—a potentially fatal cancer of the immune system—in February 2007. Rather than simply performing a transplant that would increase the patient’s chance of cancer survival, Gero Huetter, MD, of the University Medicine Berlin and his colleagues opted to perform a transplant that might also increase the patient’s chance of surviving HIV. 

Huetter asked the blood and tissue bank if any of its stem cell donors had a particular genetic defect, called the CCR5 delta-32 deletion. This defect prevents CD4 cells from developing a receptor, called CCR5, on their surfaces. People who inherit this genetic mutation from both parents have CD4 cells that lack the CCR5 entirely and, as a result, are highly resistant to HIV. People who inherit the mutation from one parent can be infected, but because they have fewer CCR5 receptors on their CD4 cells, tend to have slower disease progression.

Huetter scored an excellent match—a suitable donor with the delta-32 deletion from both parents.

As is standard in stem cell transplants, Huetter’s team prepared the patient to receive the cells by first ablating, or destroying, most of his immune cells. This process, also called conditioning, is usually performed using intensive chemotherapy and radiation. The patient also began taking a number of immune-suppressive drugs to reduce the risk of graft-versus-host disease (GVHD) following the transplant.

On the day of his transplant, he discontinued his antiretrovirals.

About 13 months after receiving the transplant, the patient’s leukemia relapsed yet again. A second round of conditioning, followed by another transplant with stem cells with the CCR5 delta-32 deletion, was performed. This led to a complete remission of the cancer.

At no point during the initial 20-month follow-up period did the Berlin Patient’s HIV rebound, as highlighted during the initial CROI presentation and in a detailed case report published in a February 2009 issue of The New England Journal of Medicine. 

However, uncertainty remained over whether a bona fide cure for HIV infection had been achieved in this patient. First, it was assumed that traces of HIV remained in the patient’s body, despite intensive pre-transplant conditioning. Second, CXCR4-targeting HIV—virus capable of using another receptor on CD4 cells—was found in the patient’s blood before conditioning and transplantation. In turn, it was suggested that archived CXCR4-targeting HIV would proliferate and become detectable, especially with the discontinuation of immune-suppressive drugs potentially keeping existing cellular reservoirs of HIV in check.

According to the December 8 report, written three-and-a-half years following the initial transplant and several months after the discontinuation of immune-suppressive treatment, the patient’s CD4 count has returned to normal—it is well within the range of HIV-negative, immune-competent individuals. What’s more, HIV remains continuously undetectable, not only in blood plasma but also in blood cells. As the article states: “Today, by monitoring the most common prognostic markers, i.e., plasma viral load and CD4+ T cell counts in the peripheral blood, HIV disease cannot be assessed in this patient.”

Additional findings used by Huetter’s team to bolster the claim that this patient has, in fact, been cured—earlier reports by Huetter and his colleagues were resistant to use the term “cure” as an outcome, based on lingering concerns—were also published. First, the researchers demonstrated successful reconstitution of CD4s throughout the body, notably in the gut, which is a common site of infection and cellular depletion in people with active HIV infection. Second, many of the HIV-negative cells collected post-transplantation were activated “memory” CD4 cells, which are the preferential targets of HIV and susceptible to infection with CXCR4-targeting virus. Lastly, during the process of immune reconstitution, Huetter’s team found that long-lived cells belonging to the patient were gradually replaced with the donor’s cells, suggesting that the any lingering population of HIV-infected cells was continuing to decrease in size.

“In summary,” the authors write, “our results demonstrate successful CD4+ T cell reconstitution at the systemic level as well as in the [gut] following [transplantation], and additionally provide evidence for the reduction in the size of the potential HIV reservoir overtime. Although the recovered CD4+ T cells are susceptible to infection with X4 HIV infection, the patient remains without any evidence for HIV infection since more than 3.5 years after discontinuation of ART. From these results, it is reasonable to conclude that cure of HIV infection has been achieved in this patient.”

Search: Berlin Patient, Hutter, Huetter, CCR5, transplant, ablation, conditioning, cure, Timothy Ray Brown

Scroll down to comment on this story.

Previous Comments:

J Clark, Phoenix, AZ, 2011-06-10 04:15:18
This is something I've wondered about for years. People with an immunity, and believe me there are, to be the answer to the vaccine and or stem cell source to finally end this nightmare disease. But why hasn't anybody thought of this before? So many have been lost. I'd even volunteer as a immune donor because I am still HIV- and was very careless in my 80's youth.

mioke, bklyn newyork, 2011-05-12 07:30:54
thank the powers that be a cure for timothy

Habiba, lagos city, 2011-05-09 17:09:08
i beleve the are holding back hiv cure and dis is not fair

Johnn, london, 2011-04-03 03:12:53
Gc-maf works... please take a look at ICAR 2011 in Florence Italian annual AIDS meeting . One patient, 44 years old, has been diagnoseg hiv+ since 1984, and full blown aids in 2001. In 2009 this patient developed resistance to conventional antiretroviral ARV and observed a decline of cd4 to 40 cells/ml and general health, and viremia arise up to 160.000 copies/ml After only 10 injections of Gc-maf, at the end of 2010, viremia decreased to 2343 copies/ml and cd4 increased up to 298 copies/ml.

Dave, Dublin Ireland, Dublin, 2011-03-04 21:05:53
I think stem Cell is the only way out, for researchers to have gone that far, then we all have hope in this century. HIV/AIDs will have cure soon! this i beleived so much.We looking forward for more versatile research on stem cell.

Acacious, Los Angeles, 2011-02-26 04:51:24
There must be competent doctors who perform marrow transplants, and delta 32 potential donors who could both stand to earn what hiv people are willing to pay for this procedure. I wouldnt be surprised if it's already happening, very quietly.

Ken, Wichita, 2011-02-20 21:16:05
The ablation was necessary for the leukemia, but I'm wondering if the CCR5 delta-32 deletion stem cells alone introduced into the system (over time) would have led to the same (or similar) results... no evidence of HIV. Not all HIV was was removed from the patient's body at the time of transplantation. Since it wasn't all removed (but substantially lessened) would a the same or a larger transplant of stem cells yield the same result without the need for ablation? Ablation is dangerous.

Katie, Philadelphia, 2011-02-09 19:23:36
Check out the blog post we just wrote-NAPWA has decided NOT to advocate for AIDS cure research during the national AIDS lobby event Feb 16-18 www.blogs.poz.com/aidspolicyproject/2011/02/is_aidswatch_keeping.html It would be great if you could weigh in at the end of that blog post in the comments section. PS-New research at UNC, Penn and UC Chapel Hill is trying to doctor up patients' own immune cells to mimic the Berlin Patient case--but if successful it would be much safer.

Bill, Washington, DC, 2011-02-08 08:44:38
Before leaping to conclusions about cover-ups and genocide, remember that this was an *extremely* risky and experimental procedure. The results, while good, were somewhat unexpected. Many transplant patients do not even survive ablation.

Ben, never never land, 2011-01-29 12:29:27
oddly i told thid to my doc and he said i was delusional until he went to a conference last week and yes as of last week after years of biopsies it is the cure. Wahts has been said is hiv pos people would not do such a risky procedure sounds like a load of crap to me their withholding the cure doesnt that qualify as genocide

celestine peterson, raleigh, 2011-01-17 21:09:50
this might be want we have been waiting for, a break thogh,but still a long way from a cure.

John, Ny, 2011-01-16 13:34:57
Im taking kpax, stem cells seem promising, assymptomatic for greater than 10 years, bs biology, 31 yo, hiv negative friend willing to test for stem cell mutation, clinical trials?

Arturo Jackson, Sacramento, CA, 2011-01-14 08:03:41
I agree with Richard of Seattle that this is huge news and why isn't it on any local or national news broadcasts..are we back to the days of population groups affected by AIDS as being "undesirables" which is why President Reagan didn't even say the word AIDS until 5 years into the epidemic!

chris robson, , 2011-01-02 19:39:17
i have been wondering if this accidentle discovery will be squashed by corporate greed or delayed by global hysteria to demand immediate trials?

teri, new port richey fl, 2010-12-28 14:48:10
I think we will have a cure in my lifetime and im 59. I hope this happens. Im in collage for nursing and I want to work with HIV people. But please how about hetrosexural people, its always about gays. Thankyou