June 12, 2012
HIV Material Detected in Berlin Patient Samples Spurs Cure Questions, Confusion
by Tim Horn
Does a recent conference presentation noting that HIV genetic material has been detected at low levels, in a minority of recent samples taken from Timothy Brown, a.k.a. “the Berlin Patient,” debunk the conclusion that he has been cured of the infection? While one scientist is publicly arguing that Brown “still has detectable HIV in his body” and goes so far to suggest that he may even have been reinfected, others—including the original study presenters—counter that these claims misrepresent the new data and are therefore misleading.
Brown is widely known as the first person with confirmed HIV infection to be cured of the virus. This occurred after he received high-dose chemotherapy to wipe out his existing immune system followed by stem cell transplants from a donor resistant to one of two forms of the virus (HIV that uses the CCR5 receptor, as opposed to the CXCR4 receptor, to gain entry into CD4 cells). His cure, first suggested as a possibility at the 15th Conference on Retroviruses and Opportunistic Infections in Boston in 2008, was ultimately declared as such in a December 2010 follow-up report published in Blood.
At various time points since undergoing the transplants, Brown has donated numerous specimens for testing, all of which have yielded encouraging results: His blood and cerebrospinal fluid (CSF) viral loads have remained undetectable; infectious virus hasn’t been detected in his bone marrow or blood-based cells (PBMCs); his HIV-specific antibody levels have trended downward; and his CD4 cell counts, both in the blood and gut, have normalized.
Whether or not Brown’s HIV has truly been eradicated (a sterilizing cure, with all traces of the virus removed from his body) or more simply controlled (a functional cure, where HIV is still present but unable to cause disease, even in the absence of antiretroviral therapy) has been difficult to determine, however, given the limits of technology to detect trace amounts of the virus in the human body.
To explore this further—and, importantly, to more fully evaluate the strengths and weaknesses of laboratory assays that will be needed in HIV eradication research—teams of researchers representing six different HIV laboratories received new blood, cell, rectal and spinal tap samples from Brown.
Preliminary results were reported by Steven Yukl, MD, on Friday, June 9, at the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies in Sitges, Spain.
According to Yukl’s presentation, most assays conducted by the six laboratory teams were HIV negative. And importantly, no infectious virus—virus capable of reproducing—was found in any of the samples tested by the six laboratories.
Neither HIV RNA nor HIV DNA was detected in PBMC samples, analyzed by four labs. At the lab where rectal samples were tested, HIV RNA was not detected. And at two labs conducting CSF tests, no viral DNA or RNA was detected. The researchers also confirmed an ongoing decline in Brown’s HIV antibody levels, now below the level of detection using commercially available assays.
Two of the laboratories did, however, detect HIV RNA in some blood plasma samples, though the actual level was too low to be accurately measured by one lab and extremly low at the other lab compared with what is typically seen in people living with HIV on successful antiretroviral treatment (less than a half copy per milliliter of blood plasma versus 1 to 2 copies per milliliter of blood plasma, respectively). HIV DNA was also found in some rectal samples by one laboratory, though the level was 8 copies per 1 million cells, which is substantially lower than the 780 per 1 million cells typically seen in viral load-suppressed people living with HIV. The researchers also noted in their conference abstract that the sequences of the HIV RNA found in the plasma samples differed from those present before Brown’s transplant, and from each other.
The latter set of findings prompted one researcher, Alain Lafeuillade, MD, an HIV cure researcher at the General Hospital in Toulon, France, and the University of Maryland, to publish a hiv-reservoir.net blog post dubbed “The Weird Story of the Berlin Patient” and a press release questioning Brown’s cure.
“The only case of a possible sterilizing HIV cure has been challenged today at the 2012 resistance workshop: the patient, actually, could still be HIV infected!” reads the headline of Lafeuillade’s blog post.
The study authors specified that it is “impossible to conclude that the subject remains HIV infected,” given the low levels of virus detected and the limits of available technology to successfully identify trace amounts of HIV genetic material in the human body.
But Lafeuillade questions the study authors' conclusions, and he offered up two alternative theories. He suggests: “First, the patient has never been cured and is a chimera. Second, he has been cured but reinfected,” noting that Brown’s rectal tissue was negative for HIV DNA using earlier post-transplant biopsy specimens and the “fact that different circulating viral strains were isolated.”
Yukl and his colleagues disagree with Lafeauillade’s take on the data. “We weren’t trying to say HIV was still there or he hadn’t been cured,” Yukl told Jon Cohen of ScienceInsider.
In fact, Yukl’s team notes in the study’s conclusion that assay contamination may have resulted in false-positive HIV RNA detection—which may also explain the gene sequence variations—in the plasma samples. Douglas Richman, MD, who heads the University of California, San Diego, lab participating in the study and whose team did not find any HIV RNA or DNA in the provided samples, concurs. “If you do enough cycles of PCR,” he told ScienceInsider, “you can get a signal in water for pink elephants.”
Tae-Wook Chun, MD, of the National Institute of Allergy and Infectious Diseases, agrees that nothing is certain. Though Chun’s group did find low levels of HIV genetic materials in some of the samples provided, he told ScienceInsider, “I don’t really know what to make of it, other than [Brown is] controlling viral replication or he doesn’t have HIV that can restart the infection. It’s a difficult case to talk about.”
All researchers involved agree that additional research is necessary, not only to shed further light on the specifics of Brown’s case, but also to better define the laboratory markers that will be needed in the hunt for both sterilizing and functional cures.
“[Brown has] been off ARVs for five years,” Richman told ScienceInsider. “That trumps all these assays.”
Search: hiv, cure, timothy brown, berlin patient, pbmcs, hiv rna, hiv dna, lafeuillade, eradication, sterilizing, functional, sitges
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comments 1 - 15 (of 18 total) next
Andy, Clearwater, 2012-08-16 05:41:54
Now there has been reports of another person cured of HIV. Weather Tim has been sterilized or functionally cured, it is a great thing! It eliminates the need for drug therapy and that is important as living on drug therapy is debilitating! There's also the issue of certain people and the pharmas doing every imaginable thing to wipe out any effort or evidence of a cure! Had this happened in America instead of Germany, we wouldn't even be hearing about it!!
yago, Barcelona, 2012-07-03 04:06:34
5 years off meds is a cure!. May be all of that is an excuse tu stop funding the cure research!. ...
Keith, Dublin, 2012-06-24 20:26:53
If it is a sterilizing cure or functional is irrelevant
There are two questions which this
A)Is HIV having a negative effect on him, has he HIV related issues
B) Can he spread the disease
That last one will be inportant for any new treatments and or cures.
Can you remove the possibility of spreading the disease or if there is a cure will you be healthy but a silent carrier.
That is a question that will need to be answered.
Timothy Brown, San Francisco, CA, 2012-06-22 00:46:40
Inwant to thank Tim Horn for an excellent article! I believe that the last sentence sums it up...
Andy, , 2012-06-17 01:45:22
LOL - this report never would have happened if a report a few days earlier wasn't released saying Tim Brown was cured. Do they actually expect people to believe this? Of course the pharma companies don't want a cure - they'd lose close to a trillon dollars if there was and that - every year. No different than the guys who wanted to put Lazurus to death so they could say he hadn't been raised from the dead in the first place. Just using that as an example of how corrupt the rich and powerful are!
Alex, Toronto, 2012-06-17 01:39:08
I hope HIV becomes Airborne, then I'm sure pharmaceuticals wold think twice from preventing a cure for HIV to be present for public use.
Alex, Toronto, 2012-06-17 01:30:17
5 years of being off the HIV Meds is proof enough that Mr. Brown does Not have HIV. He has Immunity to HIV. Just like when you get vaccinated. Those who are vaccinated can show false reading of the illness though it is not percent in the blood. Are people that stupid? I know that if I came off my HIV meds now, I know that the undetectable counts I have will emerge and increase within few months, forget 5 years. This man has been off the HIV Meds for 5 Years.
Rel, , 2012-06-15 10:48:49
its only be 5 years. It's possible to test positive for a lot of past exposures. Thats how we test for vaccines ya know lol.. smh scientists
Mary, Ouagadougou, 2012-06-15 07:33:13
Of cause do you expect the pharmaceutical companies to say someday ''here's the cure'' get a life ya all there is a cure but hidden all bcos they never want the money to stop flowing, but i tell you what........ when you die i hope you be buried along with all the riches you made i.e if not reduced to ashes in the name of cremation.
Tyrone, Bombay, 2012-06-14 22:41:50
Is it possible that pharmaceutical companies do not wish to have a cure and hence this report? They wish to continue selling their ARVs and hope there is NO CURE? Or is there a political agenda here? One would never understand. I however have faith and believe that he is CURED.
Harry, New York, 2012-06-14 22:33:31
There is still hope! Nothing has been proven against this case. But taking three pills daily.....appears to be the next best thing to a cure.
Mike, Hollywood FL., 2012-06-14 17:28:18
Regardless as to wether or not he is cured, it stands as a ray of hope to the rest of us and to the futures of millions of young people around the world, thanks for the report.
polypagan, Berea, KY, 2012-06-14 13:36:06
This is difficult to understand and very important to understand information. Of course it is possible that Mr. Brown has been re-exposed. I hope he is willing to be honest about that. It seems unlikely, though, doesn't it?
More likely, to my way of thinking, is that this finding points to important new information about how HIV infects body tissues. Alternatively, it's just a fluke.
Yeah, further study. I'm all for it!
mark, SA, 2012-06-14 13:16:27
Why researchers are so interdicting themselves as if they don't want to eradicate this disease. Focus on finding a cure
Rick Machado, Sacramento, CA., 2012-06-14 12:46:18
comments 1 - 15 (of 18 total) next
As one who has watched two partners die of HIV disease I find this story remarkable. One partner was totally non-compliant with his dozens of pills and died at 33, the other was the most voracious pill taker and followed doctors suggestions to the letter and died at 39. The latter had a far better health pattern to the end. I'm undetectable on a 3 pill regimen and have been for six years. After 25 years of HIV, I consider that a cure.
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