June 5, 2011

Advances Mean Possible End To AIDS

Timothy Ray Brown, an HIV-positive American, known as "the Berlin patient," has become an icon for the potential end of a disease that has claimed the lives of countless millions, and has also become a sign of hope for scientists who are trying to end the AIDS pandemic.

Remarkable scientific advances since HIV was first discovered 30 years ago this week mean the virus is no longer a death sentence. Thanks to tests that detect HIV early on, new drugs that have been developed that can control the virus for decades, and a variety of ways to keep it from being spread, 33 million plus HIV positive people worldwide are learning to live with the disease.

But while people can live longer lives now with HIV, the global scientific community is setting out with a new outlook on trying to find a cure. The drive is partly about science, and partly about money. Lifelong treatment of the disease with sophisticated drugs is becoming very unaffordable.

Care for HIV patients in developing countries alone already costs $13 billion a year and could triple that over the next 20 years.

Francoise Barre Sinoussi, Nobel prize winner for her work in identifying Human Immunodeficiency Virus (HIV), said that in tough economic times, there exists great need to find a cure.

"We have to think about the long term, including a strategy to find a cure," she said. "We have to keep on searching until we find one."

The Berlin patient is proof they could. His case has given renewed energy into a field where people for years believed talk of a cure was irresponsible.

Brown was living in Berlin when, besides being HIV-positive, he had a relapse of leukemia. He was dying, when in 2007, his doctor, Gero Huetter, made a radical suggestion: a bone marrow transplant using cells from a donor with a rare genetic mutation, known as CCR5 delta 32. Scientists had known for a few years that people with this gene mutation had proved resistant to HIV.

"We really didn't know when we started this project what would happen," Huetter, an oncologist and hematologist who now works at the University of Heidelberg in southern Germany, told Reuters. The treatment could have killed him. But instead, he remains the only human ever to be cured of AIDS.

"He has no replicating virus and he isn't taking any medication. And he will now probably never have any problems with HIV," said Huetter.

Most experts, however, say it is inconceivable Brown's treatment could be a way of curing all patients. The procedure was expensive, complex and risky. To do this in others, exact match donors would have to be found in a small proportion of people, most of which are of northern European descent, and have a mutation that makes them resistant to the virus.

Dr Robert Gallo, of the Institute of Virology at the University of Maryland, put it bluntly. "It's not practical and it can kill people," he said last year.

"It's clearly unrealistic to think that this medically heavy, extremely costly, barely reproducible approach could be replicated and scaled-up ... but from a scientist's point of view, it has shown at least that a cure is possible," Sinoussi noted.

The International AIDS Society this month will formally add the goal of finding a cure to its HIV strategy of prevention, treatment and care.

A group of scientist-activists is launching its own global working group to bring a scientific plan of attack to the table and persuade governments and research agencies to commit more funds to HIV and AIDS research.

The U.S. National Institutes of Health is asking for proposals for an $8.5 million collaborative research grant to search for a cure, and the Foundation for AIDS Research, or amfAR, has just announced its first round of four grants to research groups "to develop strategies for eradicating HIV infection."

Until recently, HIV and AIDS groups feared that directing funds toward a search for a cure risked seeding at least some of that money from the fight to get HIV-positive people treated. Even today, only just over 5 million of the 12 million people who need the drugs actually get them.

HIV was discovered in 1981, when the U.S. Centers for Disease Control and Prevention discovered it was the cause of AIDS. The CDC reported in its weekly Morbidity and Mortality journal that five young active homosexuals were the first documented cases of the virus.

"For the world it was the beginning of the ear of HIV/AIDS, even though we didn't know how it was HIV then," says Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, who has made AIDS research his life's work.

The disease has been ignorantly branded "the gay plague" and has become one of the most vicious pandemics in human history. Transmitted in semen, blood and breast milk, HIV has devastated poor countries and regions, particularly sub-Saharan Africa, where the vast majority of HIV-positive people live.

But as more tests and treatments have become available, the number of new infections has been dropping. But for every two with HIV who get a chance to start on AIDS drugs, five more become newly infected. United Nations data shows that despite the available prevention measures more than 7,100 people catch the virus every day.

Treatment costs can range from $150 a year per person in poor countries to as much as $20,000 a year in the United States. The costs are huge. A recent study as part of a non-governmental campaign called AIDS2031 suggests that low and middle-income countries will need $35 billion a year to address the pandemic by 2031.

"It's clear that we have to look at another possible way of managing of the epidemic beyond just treating everyone forever," said Sharon Lewin, a leading HIV doctor and researcher from Monash University in Melbourne, Australia.

In the disease's early days, scientists looked for possible cures, but their attempts were thwarted when they discovered HIV could lie low in pools or reservoirs of latent infection that even powerful drugs could not reach.

"Scientifically we had no means to say we were on the way to finding a cure," says Bertrand Audoin, executive director of the Geneva-based International AIDS Society. "Scientists ... don't want to make any more false promises. They didn't want to talk about a cure again because it really wasn't anywhere on the horizon."

And even while now it is unlikely for an easy cure to be found anytime soon, Brown's case has opened the door to new ideas. "What it proved was that if you make someone's cells resistant to HIV...then all the last bits of HIV, that hang around for a long time in patients on treatment, did in fact decay and disappear," said Lewin.

Scientists are now working on trying to mimic the effect of the Berlin patient's transplant and have had some success. One experimental technique uses gene therapy to take out certain cells, make them resistant to HIV and then put them back into patients with the hope they will survive and spread.

At an HIV conference in Boston earlier this year, American researchers presented data on six patients who had large numbers of white blood cells known as CD4 cells removed, manipulated to knock out the existing CCR5 gene, and then replaced.

"It works like scissors and cuts a piece of genetic information out of the DNA, and then closes the gap," said Huetter. "Then every cell arising from this mother cell has this same mutation."

Initial results showed the mutated cells managed to survive inside the bodies of the patients at low levels, remaining present for more than three months in five. "This was a proof of concept," said Lewin.

Another potential technique is a small group of patients known as "elite controllers," who despite being infected with HIV are able to keep it under control simply with their own immune systems. Researchers hope these patients could one day be the clue to developing a successful vaccine or functional cure for HIV/AIDS.

Scientists are also looking into ways they can "wake up" HIV cells and kill them. As discovered in the late 1990s, HIV has a way of getting deep into the immune system itself -- into what are known as resting memory T-cells -- and going to sleep there. Hidden away, it effectively avoids drugs and the body's own immune response.

"Once it goes to sleep in a cell it can stay there forever, which is really the main reason why we can't cure HIV with current drugs," Lewin told Reuters. Her team in Melbourne and another group in the United States are about to start the first human trials using a drug called SAHA or vorinostat, made by Merck and currently used in cancer treatment, which has shown promise in being able to wake up dormant HIV.

Seth Berkley, a medical epidemiologist and head of the U.S.-based International AIDS Vaccine Initiative (IAVI) is concerned that talk of a new cure could bring up the old question of whether it is the right goal to follow.

"From a science point of view, it's a fabulous thing to do. It's a great target and a lot of science will be learned. But from a public health point of view, the primary thing you need to do is stop the flow of new infections," said Berkley. "We need a prevention revolution. That is absolutely critical."

South African activist Vuyiseka Dubula agrees. She finds talk of a cure for HIV distracting, almost disconcerting. "This research might not yield results soon, and even when it does, access to that cure is still going to be a big issue," she said. "So in the meantime, while we don't have the answer on whether HIV can be cured or not, we need to save lives."


On the Net:

Institute of Virology

International AIDS Society

U.S. Centers for Disease Control and Prevention

U.S. National Institutes of Health

Foundation for AIDS Research