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EPIDEMICS
AIDS cure may have two main pathways: experts
by Staff Writers
Washington (AFP) July 24, 2012


Cancer drug flushes out lurking AIDS virus: study
Paris (AFP) July 25, 2012 - Scientists in the United States said Wednesday they had used a cancer drug to flush out the AIDS virus lurking dormant in trial patients' white blood cells -- a tentative step towards a cure.

The ability of the HIV genome, or reproductive code, to hide out in cells and be revived after decades poses a major obstacle in the quest for a cure.

Being able to expose the virus in its hiding place would allow scientists to target the host white blood cells in a killing blitz.

"It is the beginning of work toward a cure for AIDS," David Margolis, co-author of the study published in the journal Nature, told AFP as the International AIDS Conference was under way in Washington.

HIV is a retrovirus, inserting its DNA into the genome of host white blood cells, CD4+T cells in this case, and turning them into virus factories. Sometimes it goes into hiding in some cells even as others keep on producing.

Some 34 million people around the world are living with HIV, which destroys the immune system and has caused about 30 million AIDS-related deaths since the disease first emerged in the early 1980s.

In the latest study, researchers in the United States used the chemotherapy drug vorinostat to revive and so unmask latent HIV in the CD4+T cells of eight trial patients.

The patients were also on antiretroviral drugs, which stops HIV from multiplying but have to be taken for life because they do not kill the virus hidden away in reservoirs.

"After a single dose of the drug, at least for a moment in time, (vorinostat) is flushing the virus out of hiding," Margolis said of the trial results -- the first drug ever shown to do so.

"This is proof of the concept, of the idea that the virus can be specifically targeted in a patient by a drug, and essentially opens up the way for this class of drugs to be studied for use in this way."

The drug targets an enzyme that allows the virus to lie latent.

The researchers cautioned that vorinostat may have some toxic effects and stressed this was merely an early indication of feasibility that had to be explored further.

Exactly what would happen after the virus was unveiled in reservoir cells was also not certain, said Margolis.

"We know that many cells that produce HIV die in the process. We know many cells that produce HIV can be identified and killed by the immune system. As far as we can tell, all the viruses floating around while patients are taking therapy don't get into cells because they are blocked by the therapy," he said.

Without a host cell, the virus would die within a few minutes.

"There is a possibility that this could work. But ... if it is only 99 percent true and one percent of the virus escapes, it won't succeed. That is why we have to be careful about our work and what we claim about it."

In a comment published with the study, HIV researcher Steven Deeks said the research provided "the first evidence that ... a cure might one day be feasible".

But, as is common with early clinical trials, the study raised more questions than answers -- including ethical concerns about giving potentially toxic drugs to HIV-infected people who are otherwise healthy, he said.

"These data from the lab of David Margolis are genuinely exciting for those exploring pathways to achieving a cure for AIDS," Oxford University HIV researcher John Frater told AFP, calling for investment in further research.

HIV immunologist Quentin Sattentau called the findings promising, but said other types of reservoir cells, including in the brain, may not respond to this treatment.

"Thus there is a long way to go before we will know if this can work to completely eradicate HIV from an infected person."

Investigators are looking into two main paths toward a cure for AIDS, based on the stunning stories of a small group of people around the world who have been able to overcome the disease.

Despite progress in treating millions of people globally with antiretroviral drugs, experts say a cure is more crucial than ever because the rate of HIV infections is outpacing the world's ability to medicate people.

"For every person who starts antiretroviral therapy, two new individuals are infected with HIV," Javier Martinez-Picado of the IrsiCaixa AIDS Research Institute in Spain told the International AIDS Conference in Washington on Tuesday.

Some 34 million people around the world are living with HIV, which has caused around 30 million AIDS-related deaths since the disease first emerged in the 1980s.

While antiretroviral drugs are helping more people stay alive than ever before, they are costly and must be taken for life. Experts say only a cure or a vaccine can make a sufficient dent in the deadly pandemic.

While a cure certainly remains years away, Martinez-Picado said scientists can now "envision a cure from two different perspectives," either by eradicating the virus from a person's body or coaxing the body to control the virus on its own.

The most extraordinary case of an apparent cure has been seen in an American man, Timothy Ray Brown, also known as the "Berlin patient," who was HIV-positive and developed leukemia.

Brown needed a series of complex medical interventions, including total body irradiation and two bone marrow transplants that came from a compatible donor who had a mutation in the CCR5 gene, which acts as a gateway for allowing HIV into the cells.

People without CCR5 appear to be resistant to HIV because, in the absence of that doorway, HIV cannot penetrate the cells.

"Five years after the (first) transplant, the patient remains off antiretroviral therapy with no viral rebound," said Martinez-Picado.

"This might be the first ever documented patient apparently cured of an HIV infection."

However, while the case has provided scientists with ample pathways for research on future gene therapies, the process that appears to have cured Brown carries a high risk of death and toxicity.

"Unfortunately this type of intervention is so complex and risky, it would not be applicable on a large scale," Martinez-Picado said.

Brown, 47, announced Tuesday he was launching his own foundation to boost research toward a cure as the US capital hosts the world's largest scientific meeting on HIV/AIDS.

"My plan is basically to find donors to get funds to help research and set up a system to decide who gets the money," said a frail-looking Brown, 47, adding that he planned to dedicate his life to finding a cure for others.

"I am living proof that there could be a cure for AIDS."

Another group of intense interest is known as the "controllers," or people whose bodies appear to be able to stave off HIV infection.

One type, known as the "elite controllers," test positive for HIV but do not appear to have the virus in the blood, even without treatment. Researchers estimate there may be a few hundred of these people in the world.

Post-treatment controllers are people who started therapy early and are able to stop it without seeing the virus rebound. Some five to 15 percent of HIV-infected people may fall into this category.

More details on a group of "controllers" in France known as the Visconti Cohort are expected to be released at the meeting this week, as international scientists share their latest data in the hunt for a cure.

Martinez-Picado also described a "promising" study by US researchers, published in the journal Nature, that looks into using new drugs to get rid of the virus when it holes up, or lies dormant in the immune system.

Led by researchers at the University of North Carolina, the small study on eight HIV-positive men taking antiretrovirals probed how the lymphoma drug vorinostat could activate and disrupt the dormant virus.

Patients who took the drug showed an average 4.5-fold increase in the levels of HIV RNA in their CD4+ T cells, evidence that the virus was being unmasked and demonstrating a new potential strategy for attacking latent HIV infection.

Last week, international researchers announced a new roadmap toward a cure, calling for more funds and a renewed focus on curing AIDS, led by Nobel laureate Francoise Barre-Sinoussi, the co-discoverer of HIV.

"We now actively talk of potential scientific solutions in a way perhaps we weren't some years ago," said Diane Havlir, AIDS 2012 US co-chair and professor of medicine at the University of California, San Francisco.

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