Leukemia drug could 'cure' HIV, say researchers



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Trials on four infected monkeys showed that twice the arsenic trioxide had not detected detectable virus levels 80 days after treatment.

Trials on four infected monkeys showed that twice the arsenic trioxide had not detected detectable virus levels 80 days after treatment.

A leukemia drug can completely rid HIV-positive people of the virus that slowly leads to AIDS, say the scientists.

Trials on four infected monkeys showed that twice the given arsenic trioxide showed no detectable level of the virus 80 days after treatment.

The other two had fewer viruses in their body, but not enough to be technically classified in remission.

None of the macaques – who received a strain of HIV similar to that which strikes humans – took any other drugs designed to keep the virus at bay.

Experts hope this breakthrough could cure the 37 million people living with the virus in the world.

Charities say it could replace a risky procedure that simultaneously fights cancer and has already cleared two patients of the virus.

But they warned that the study on macaques, which they described as "promising", is still preliminary and needs to be deepened.

Shaffiq Essajee, UNICEF Advisor for HIV / AIDS, told MailOnline: "The findings of the recent study are very interesting and suggest that new drugs, combined with existing antiretrovirals, could reduce or eliminate HIV reservoir.

"These findings warrant further research to evaluate the safety and effectiveness of this approach for people living with HIV, especially children."

Doctors are currently testing a stem cell transplant that has cleared at least two patients of the virus in the long term. He is known to be dangerous.

The details about the newest patient – known as the "London Patient" – were only made public in March at a medical conference in Seattle.

The patient, who had Hodgkin's lymphoma, had had the stem cell transplant of the last resort of a donor carrying an HIV-resistant gene.

After 18 months, the man showed no evidence of HIV status, although he chose not to take antiretroviral drugs (ART) to keep his virus at bay.

Antiretroviral therapy, taken daily, suppresses the virus to prevent a resurgence. Within six months of taking the tablets, the virus can be reduced to undetectable levels.

After a few weeks of treatment, the rate of virus in patients can explode.

Man is not considered cured – only in long-term remission. For example, cancer patients must be in remission for five years before being labeled as cured.

Experts hope this breakthrough could offer hope to 37 million people living with the virus worldwide (image in stock)

Experts hope this breakthrough could offer hope to 37 million people living with the virus worldwide (image in stock)

However, the experimental procedure – which involves transmitting to the genes of patients from people naturally immunized against HIV – is dangerous because patients can undergo a fatal reaction if the immune replacement cells do not take it.

Critics also say that this does not apply to most people living with HIV, as this would only benefit a handful of cancer patients.

The new approach, involving a drug already approved in the United States and Europe, could be used or lead to a substitute for the stem cell risk procedure – which also works for patients who are not already suffering from cancer.

Researchers from King & # 39; s College London and the Chinese Academy of Sciences have given four HIV-positive monkeys, arsenic trioxide.

Two of the monkeys showed signs of complete suppression of the virus, according to the report published in the journal Advanced Science.

Neither of them experienced a "rebound" – when the virus becomes detectable again – when all their antiretroviral treatments have been stopped.

The other two showed signs of watering the virus but not enough to prevent a rebound, according to the results.

The researchers, led by Dr. Qing Yang, showed that the drug approach could mimic the second phase of the risky stem cell transplant.

Phase two works by reducing the number of immune cells on which HIV receptors are activated. However, it is not known how diarsenic trioxide does this.

During transplants, patients receive stem cells from individuals with a mutated CCR5 gene, so their white blood cells have incomplete receptors, preventing the HIV virus from entering and infecting cells. CCR5 is the gene that HIV targets and uses as an access point to enter the immune system.

Further tests are needed to confirm the new findings before the drug is tested on humans.

Researchers first showed that arsenic trioxide could replicate the first phase of stem cell therapy more than a decade ago, but on a more moderate scale.

In laboratory tests, they discovered that he could kill the immune cells harboring HIV without touching the virus-free cells.

Timothy Ray Brown, known in the medical community as the "Berlin patient", has been HIV-free for 12 years without medication

Timothy Ray Brown, known in the medical community as the "Berlin patient", has been HIV-free for 12 years without medication

HOW HAS A STEM CELL TRANSPLANT CURED THE BERLIN PATIENT AND THE LONDON PATIENT?

By Mia de Graaf, health editor for DailyMail.com

The vast majority of humans carry the CCR5 gene.

In many ways, it's incredibly useless.

According to recent research, this affects our chances of survival and healing.

And this is the main point of access for HIV to overcome our immune system.

But some people carry a mutation that prevents CCR5 from effectively expressing, blocking, or eliminating the gene.

These few people around the world are termed "elite controllers" by HIV experts. They are naturally resistant to HIV.

If the virus ever entered their body, they would naturally "control" the virus as if they were taking the virus-suppressing drugs needed by HIV patients.

Both Berlin and London patients have received stem cells from people with this crucial mutation.

WHY HAS EVER WORKED BEFORE?

"There are many reasons why it has not worked," Dr. Janet Siliciano, a leading HIV researcher at Johns Hopkins University's Faculty of Medicine, told DailyMail.com. .

1. FIND DONORS

"It's incredibly difficult to find HLA-compatible bone marrow [i.e. someone with the same proteins in their blood as you]Says Dr. Siliciano.

"It's even harder to find the CCR5 mutation."

2. INJECTIVE TRANSPLANT LEADS TO CANCER RESUME

Secondly, there is always a risk that the bone marrow will not "pick up".

"Sometimes you do not become completely chimerical, which means you still have a lot of your own cells.

This is one of the two most common reasons for failure of previous attempts: their immune system is not completely replaced, then cancer reappears and they can not survive.

3. GRAFT-VERSUS-HOST DISEASE: THE OLD IMMUNE SYSTEM ATTACKS THE NEW

The other most common reason why this approach has failed is graft versus host disease.

It is at this point that the patient's immune system is attempting to attack the incoming immune system, causing a fatal reaction in most cases.

4. UNKNOWN QUANTITIES

It is interesting to note that patients in Berlin and London both had normal life-threatening complications in most other cases.

And experts believe that these complications help their cases.

Timothy Ray Brown, the Berlin patient, had both – his cancer came back and he developed a graft-versus-host disease, putting him in a coma and needing a second bone marrow transplant.

The London patient had one: he was suffering from graft-versus-host disease.

Against all odds, they both survived without HIV.

Some think that, paradoxically, graft versus host disease could have helped them further suppress their HIV.

But there is no way to control or reproduce this safely.

Researcher Marina Lusic, from a German university and another from an Italian institution, patented the HIV drug at the time.

Dr. Andrea Savarino, the other patentee, said that arsenic trioxide functions by a mechanism called "shock and kill".

The method clears the virus so that it can be attacked. This is one of the avenues explored by HIV researchers.

Dr. Savarino, of the Italian Institute of Health, told MailOnline: "Although it is still preliminary, it could be a step towards an evolutionary strategy."

He added, "The proposed therapy provides the essential building blocks of the HIV treatments seen so far.

"What is remarkable is that the desired effect can be achieved with a small molecule in place of the complex life-threatening procedure."

Commenting on the study on macaques, he said that at this stage of the research, the 50% success rate is "extremely high."

WHY IS HIV DIFFICULT TO TREAT?

In 1995, researchers discovered why HIV is able to return even though it seems to have been defeated.

The virus buries a part of itself in latent reservoirs of the body, sleeping as a "backup".

In 1996, it was discovered that antiretroviral therapy (ART) could suppress the virus and prevent its resurgence if the drug was taken under religious conditions.

But once this coverage is lifted, the virus rebuilds quickly.

Despite decades of attempts, we still do not know how to tackle these hidden parts of the virus.

The most promising approach may well be a "shock and destruction" technique: wake up the virus from its hiding place and then bombard it.

But we do not yet know how to wake him up without harming the patient.

Dr. Savarino said, "In more than a decade, only two patients [London and Berlin]and maybe a third [Düsseldorf], have managed to cure HIV.

"All the other patients unfortunately died during medical procedures or were unable to eradicate the virus after the transplant.

& # 39; The risks residing in [that] This procedure makes it impossible to apply to the majority of people living with HIV / AIDS in the world.

"At present, only one drug, arsenic trioxide, could possibly replace this procedure by minimizing the risks to the patient's health."

Dr. Savarino explained that, as arsenic trioxide is already approved for use in humans, it could be quickly converted into tests.

Dr. Savarino added, "This is good news because the way of clinical trials can be expedited because the drug is already approved for clinical use, but for another indication.

"Only one injectable form is available in Europe, which could pose few logistical problems for people living with HIV / AIDS who would like to participate in clinical trials.

"However, oral formulations are at an advanced stage of development and their availability would make more feasible a possible scale-up of the drug in case the early clinical trials yield promising results."

Diarsenic trioxide is also called Trisenox or ATO. It is administered to leukemic patients by infusion.

Cancer Research UK says that it works by speeding up the death of leukemic cells and encouraging the development of normal blood cells.

In 1995, researchers discovered why HIV is able to return even though it seems to have been defeated.

In 1995, researchers discovered why HIV is able to return even though it seems to have been defeated.

HIV TRANSMISSION AND PREVENTION

You can contract or transmit HIV only through specific activities, most often through sexual behaviors and the use of syringes or needles.

The FDA has approved more than two dozen antiretroviral drugs to treat HIV infection.

They are often divided into six groups because they work in different ways.

Doctors recommend taking a combination or "cocktail" of at least two of them.

Called antiretroviral therapy or ART, it can not cure HIV, but drugs can prolong the life span and reduce the risk of transmission.

1) Nucleoside / nucleotide reverse transcriptase inhibitors (NRTIs)

NRTIs force the virus to use faulty versions of building blocks so that infected cells can not produce more HIV.

2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NNRTIs bind to a specific protein so that the virus can not reproduce.

3) Protease inhibitors (PIs)

These drugs block a protein that forces infected cells to collect new copies of the virus.

4) Fusion inhibitors

These drugs help to prevent HIV from getting inside healthy cells.

5) CCR5 antagonist

This stops HIV before it enters a healthy cell, but in a different way from the fusion inhibitors. It blocks a specific type of "hook" on the outside of some cells so that the virus can not connect.

6) Integrase inhibitors

These prevent HIV from reproducing by blocking a key protein that allows the virus to insert its DNA into the healthy cell's DNA.

Deborah Gold, Executive Director of the National AIDS Trust, welcomed the findings, but expressed concern about the results.

She told MailOnline, "It is interesting to note that this could potentially be a fundamental element in the discovery of a simple and scalable procedure.

"But it's also clear that an HIV treatment is not something we can expect to celebrate imminently."

Ms. Gold added, "This research is too early in life to assume success.

"We welcome developments in treatment research, but we probably have enough time to wait."

Chamut Kifetew, Project Manager at Terrence Higgins Trust, said: "The preliminary results of this new research are promising.

"And it is welcome to see that there is potential that could lead to an evolutionary mechanism of HIV eradication.

"But it's really important to point out that this is a very recent research that we do not know how it would work for people living with HIV.

"So while we hope this will help us find a cure for HIV in the years to come, it will not be for quite some time."

The case of the London patient was published by the journal Nature and presented at a medical conference in Seattle.

The unidentified man has achieved a "sustainable remission" of HIV after being treated at Hammersmith Hospital in West London.

He was diagnosed with HIV in 2003. He developed Hodgkin lymphoma in 2016 and in the same year he accepted a stem cell transplant.

The patient has voluntarily stopped taking anti-HIV drugs to see if the virus will come back – which doctors generally do not recommend.

At the same conference, it was announced that a third HIV-positive patient was free of the virus after undergoing revolutionary treatment.

The "Düsseldorf patient", who was also not identified, did not show any signs of infection four months after treatment.

Doctors at the time said that the man had not shown any obvious signs of the virus long enough to be declared in long-term remission.

Timothy Ray Brown is the only other person who has survived stem cell transplantation and is coming out of it without HIV.

Mr Brown, known in the medical community as the "Berlin patient", has been HIV-free for 12 years without medication.

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