Amfar Think Tank Attendees
University of California, San Francisco University of California, San Francisco Senior Scientist for Programs, amfARWeill Cornell Medical College City of Hope
Was that a one-time meeting, or is this an ongoing think tank?
That was a one-time meeting, but due to this meeting, my editorial in The AIDS Reader6 and my commentary for amfAR, I started getting calls from transplant programs throughout the United States saying they think they have an eligible patient for this.
So, with amfAR’s blessing, a core group of transplanters was created that would make certain that we had the best protocol to treat the next eligible person that had a match. Some people from the group that I just mentioned are on this panel, but I also have additional people from Johns Hopkins University and Harvard.
The Second Person Ever Has Been Cured Of Hiv
Despite the effort being put into the fight against the human immunodeficiency viruses , only one person has ever been declared functionally cured. The success of that case has been difficult to replicate, but now scientists have declared a second person has been cured of HIV, according to a new case report published today in The Lancet HIV.
A patient previously diagnosed with HIV-1, known as the London patient, appears to have no active viral infection in their body after receiving stem cell transplantation from donors with an HIV-resistant gene. He’s now been in remission for 30 months, and mathematical modeling suggests that the probability of remission for life is extremely high.
This is a similar method used to treat the first person cured of HIV, known as the Berlin patient, who was functionally cured in 2008. Just like this case, remnants of the virus’ DNA remain in their tissue sample, although the researchers say these are essentially harmless fossils of the infection and dont appear to be capable of reproducing the virus.
We propose that these results represent the second ever case of a patient to be cured of HIV, lead author Professor Ravindra Kumar Gupta, from the University of Cambridge in the UK, said in an emailed statement.
Our findings show that the success of stem cell transplantation as a cure for HIV, first reported nine years ago in the Berlin patient, can be replicated.
I want to be an ambassador of hope.
Putting This New Report In Context
The race for an HIV cure has been a long, gradual, and often frustrating process.
Dr. Steven Deeks, a professor of medicine in residence at the University of California, San Francisco and a faculty member in the division of HIV, infectious diseases, and global medicine at Zuckerberg San Francisco General Hospital, wrote in an email to Healthline that these cases provide proof that a cure is at least feasible.
When asked to clearly define what a sterilizing cure even is, Deeks wrote that, in contrast to the Berlin and London patients, these apparent cures occurred via a natural immune response.
If we can figure out the mechanism, we may be able to come up with novel therapies that take advantage of our own defense system, one that is far safer than the bone marrow transplants that led to the previous cures, he wrote.
Dr. Hyman Scott, MPH, the clinical research medical director at Bridge HIV and an assistant clinical professor of medicine at UCSF, told Healthline its necessary to frame this report in a way to make it clear it isnt a sign of a foolproof cure.
Scientists are still unclear exactly how these two womens bodies may have rid themselves of the virus.
If those pieces can be replicated, maybe there will be a strategy down the line for vaccination, for a combination of vaccination and medication, or a combination of multiple vaccinations and multiple medications. Maybe that might be a road map, he said.
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What Are The Challenges
While research on a cure is promising, there are some challenges. One is that we donât fully understand how HIV reservoirs work. Scientists are learning how to find, measure, and destroy them.
What about stem cell therapy? The CCR5 mutation that protects you from HIV is very rare, so itâs hard to find donor cells. Also, stem cell therapy is risky. People can reject donor cells and become very ill. Scientists are trying to find therapies that make a personâs own cells resistant to the virus, so they wonât need donor cells.
Another challenge is that males are the subjects of most HIV clinical trials, but about half of people with the virus are female. We need more studies to look at whether treatments will work on women and girls.
Even though research is very promising, it could be a few years before these treatments are tested to be sure they work well and are safe to use in many people who have HIV.
What Is The Most Important Hiv Research Being Done Now To Address Finding A Cure For Hiv/aids
In your opinion, what is the most important research being done regarding curing HIV?
It’s figuring out how we take this proof of concept from one patient and do it on demand.
The ideas are out there on how to do it. Basically, what you need to do is mutate this gene in every single cell that you’re going to transplant into a person. What if we just took the person’s own cells, or that of the next available donor that walks in the door who happens not to have the CCR5 mutation — as statistically they won’t — and genetically give them the mutation?
Can we knock out the gene for CCR5? That’s called genetic engineering. We’re really good at doing genetic engineering in one cell. But the average person getting transplanted is getting a few billion cells, and we have to guarantee that 100.0 percent of those few billion cells all have their genes modified. We could take a few hundred or a few thousand cells, make certain that every single one of them has that gene modified, and then grow them into billions of cells that we can inject back into the patient, but we don’t know how to do that.
So I think it’s partly a technology problem, and that’s where research comes in. We know what we need to knock out: CCR5. We have people looking, as I mentioned earlier, for other things that might account for other people being resistant to getting infected with HIV. If we find those changes, we’ll have other targets to knock out.
It has nothing to do with their cancer?
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The Aids Activist Also Known As The Berlin Patient Represented Optimism That Scientists Could Find A Way To Beat Hiv
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ABOVE: SCOTT TABER
Timothy Ray Brown, who became the first HIV patient to be cured of the infection, died September 29 of leukemiathe very disease that led to the fortuitous eradication of the virus from his body. He was 54.
Until he disclosed his identity, Brown was known as the Berlin patient, whose HIV infection was eliminated in 2007 after undergoing a stem cell transplant to treat acute myeloid leukemia. The bone marrow donor was selected to have a naturally occurring genetic variant that blocked HIV from entering cells. The treatment workedboth for his cancer, and his viral infection.
Timothy symbolized that it is possible, under special circumstances to cure HIV, Gero Hütter, the doctor who performed the stem cell transplant, tells the Associated Press.
Until 2016, Brown remained the only person in the world to have been cured of AIDS using this approach and his unique experience motivated him to advocate for AIDS research. As he told The Scientist in 2015, I didnt want to be the only one in my club.
Within months of the transplant, the virus was gone from Browns cells, although his recovery was difficult and he required a second transplant to treat the leukemia.
Brown never again tested positive for HIV. His leukemia, however, relapsed five months ago.
The Challenge Of The Replication Cycle
Instead of being able to focus on a single strain of HIV, researchers have to account for the fact that it replicates so quickly, which can cause mutations and new strains. The replication cycle of HIV takes a little more than 24 hours.
And while the replication process is fast, it’s not the most accurateproducing many mutated copies each time, which then combine to form new strains as the virus is transmitted between different people.
For example, in HIV-1 , there are 13 distinct subtypes and sub-subtypes that are linked geographically, with 15% to 20% variation within subtypes and variations of up to 35% between subtypes.
Not only is this a challenge in creating a vaccine, but also because some of the mutated strains are resistant to ART, meaning that some people have more aggressive mutations of the virus.
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First Woman May Be Cured Of Hiv Without A Bone Marrow Transplant
Loreen Willenberg is part of a group of elite controllers whose HIV appears to be locked away where it cant produce new virus.
A California woman may be the first person to be cured of HIV without a bone marrow transplant, according to a recent report in Nature. More than 60 other so-called elite controllers, who have unusually potent immune responses to HIV, were found to have their virus sequestered in parts of their genome where it is unable to replicate.
The unusual case involves Loreen Willenberg, who acquired HIV in 1992. Her immune system has maintained control of the virus for decades without the use of antiretroviral treatment, and researchers have been unable to find any intact virus in more than 1.5 billion of her cells. Elite controllers are thought to make up less than half a percent of all people living with HIV.
I believe Loreen might indeed meet anyones definition of a cure, study coauthor Steven Deeks, MD, of the University of California at San Francisco, told POZ. Despite heroic efforts, we just could not find any virus that is able to replicate. Her immune system seems completely normal. Even her HIV antibody levels are low, which is unprecedented in an untreated person.
Xu Yu, MD, of the Ragon Institute of Massachusetts General Hospital, MIT and Harvard analyzed integrated HIV in millions of cells from 64 elite controllers and 41 typical HIV-positive people on antiretroviral therapy recruited at Mass General and San Francisco General Hospital.
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The person whose case is described in Tuesdays paper got a transplant of the stem cells that produce blood and immune system cells typically found in a persons bone marrow with this mutation from a donor about 10 percent of people in some Northern European countries naturally carry the mutation.
Like Timothy Brown, this persons transplant happened as part of his cancer treatment. After doctors diagnosed him with an advanced case of Hodgkins lymphoma, the person went through chemotherapy and a transplant from a donor picked in part for his or her CCR5 mutation.
Unlike Brown, though, this persons cancer treatment didnt involve full-body radiation, and his chemotherapy was also far gentler. Thats encouraging, but Walker, the Ragon researcher, noted the risks from even this regimen were still too great to offer these kind of stem cell transplants outside of cancer treatment. Given that the life expectancy for people with HIV on antiretroviral medications has increased dramatically and, one study found, is now a nearly normal one, theres a very high bar for subjecting people to any additional risk, he said. This wasnt without risk, but was much less .
The CCR5 mutations virus-blocking power can be simulated with a drug. Since 2007, Viiv Healthcare, a joint venture initially formed by Pfizer and GlaxoSmithKline, has marketed a drug, called Selzentry in the United States, that prevents HIV from using the CCR5 receptor by binding to the receptor itself.
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Florida Man Who Hid Hiv Status From Gal Pals Sentenced To Prison
A German man could be the third person in history to ever be cured of the HIV virus, researchers announced this week.
The so-called Düsseldorf patient case was announced Wednesday, at the Conference on Retroviruses and Opportunistic Infections in Seattle, New Scientist reported.
Biopsies from his gut and lymph nodes have shown no infectious HIV following a bone marrow transplant, and three-and-a-half months off antiviral drugs, Annemarie Wensing of the Netherlands-based University Medical Center Utrecht, who worked on the case, told the outlet.
Though doctors are optimistic about the case, its too soon to know for sure whether or not hes cured.
The development comes only days after doctors revealed that a London man was likely the second-person to recover from the virus.
The man, who was not identified, was diagnosed with HIV the virus that causes AIDS in 2003, according to the findings published by the journal Nature.
He later developed cancer and agreed to undergo a bone-marrow transplant for treatment.
Doctors found a donor with a gene-mutation that is naturally resistant to the HIV virus, according to the findings.
The patient received the bone-marrow transplant in May 2016.
He received other treatments as well, but by September 2017, he stopped taking anti-HIV drugs and has remained virus free for more than a year, the New York Times reported.
Both patients are registered to a research collaboration project called IciStem, according to a statement.
What Is The Treatment
Stem-cell transplants appear to stop the virus being able to replicate inside the body by replacing the patient’s own immune cells with donor ones that resist HIV infection.
Adam Castillejo – the now 40-year-old “London Patient” who has – has no detectable active HIV infection in his blood, semen or tissues, his doctors say.
It is now a year after they first announced he was clear of the virus and he still remains free of HIV.
Lead researcher Prof Ravindra Kumar Gupta, from the University of Cambridge, told BBC News: “This represents HIV cure with almost certainty.
“We have now had two and a half years with anti-retroviral-free remission.
“Our findings show that the success of stem-cell transplantation as a cure for HIV, first reported nine years ago in the Berlin Patient, can be replicated.”
But it will not be a treatment for the millions of people around the world living with HIV.
The aggressive therapy was primarily used to treat the patients’ cancers, not their HIV.
And current HIV drugs remain very effective, meaning people with the virus can live long and healthy lives.
Prof Gupta said: “It is important to note that this curative treatment is high-risk and only used as a last resort for patients with HIV who also have life-threatening haematological malignancies.
“Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful anti-retroviral treatment.”
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What Does All This Mean
Aside from the advancements in cure research the truth is we already have highly effective antiretroviral treatment that is giving people living with HIV the opportunity to live a near-normal life.
While this already an amazing achievement, theres more to be done to improve the lives of people living with HIV including combatting stigma, reducing pill burdens and removing sexual taboos. Cure research is just one of the ways that we can move the HIV response forward.
Success Of Stem Cell Transplantation
In this second case, the person received a stem cell transplant with cells that did not express the CCR5 gene, which produces a protein that helps the virus enter cells.
The cells without the CCR5 gene were part of a bone marrow transplant, which the person was undergoing as a treatment for Hodgkin lymphoma.
Following the transplant, and at 30 months after the person ceased antiretroviral therapy, doctors confirmed that the HIV viral load remained undetectable in blood samples.
This finding means that whatever traces of the viruss genetic material might still be in the system, they are so-called fossil traces, meaning that they cannot lead to further replication of the virus.
The specialists confirmed that HIV also remained undetectable in samples of cerebrospinal fluid, semen, intestinal tissue, and lymphoid tissue.
We propose that these results represent the second ever case of a patient to be cured of HIV, says the studys lead author, Prof. Ravindra Kumar Gupta, from the University of Cambridge in the U.K.
Our findings show that the success of stem cell transplantation as a cure for HIV, first reported 9 years ago in the Berlin patient, can be replicated.
Prof. Ravindra Kumar Gupta
However, Prof. Gupta emphasizes that t is important to note that this curative treatment is high risk and only used as a last resort for patients with HIV who also have life threatening hematological malignancies.
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But that drug has the same issues that most drugs have: It needs to be taken every day. Just like any other suppressive therapy for HIV, as soon as a person stops taking the drug, the virus comes roaring back, said Fred Hutchinsons Jerome. In an ideal world, the treatment for HIV would look more like Luxturna, a recently approved gene therapy for a form of blindness thats injected just once into a persons eye, and less like Lipitor.
The beauty of a transplantation or a gene therapy approach targeting CCR5 thats the kind of thing that looks like you can do it once, and then the persons cured, Jerome said. They dont need to worry about the virus any more, they dont need to worry about their access to drugs or remembering to take it every day.
The most infamous gene therapy experiment targeting CCR5 is undoubtedly He Jiankuis, which and, later, actual children with a CRISPR-mutated CCR5 gene. His announcement triggered a massive backlash from scientists, ethicists, and the Chinese government.
Less controversial gene editing work is ongoing, too. Sangamo Therapeutics, for example, is working on genetically editing T cells and stem cells to carry the CCR5 mutation. According to the companys pipeline chart, that treatment is in early-stage clinical trials.
The virus may still be hiding out someplace and it may come back 10 years from now, Walker noted. You can never be absolutely certain that a cure has been achieved.