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Researchers turn focus to finding a cure for HIV

 
Published July 25, 2012

An influential group of scientists gathered this week at the International AIDS Conference in Washington is committing to a goal that just five years ago would have seemed ludicrous: to cure HIV.

After studying the virus for more than 30 years and developing potent drugs that transformed the disease from a death sentence into a manageable chronic condition, a growing number of researchers now say the search for a cure should be a major research priority.

Recent medical and scientific advances — including the case of the first man definitively cured of the human immunodeficiency virus — offer proof that it's possible, researchers say.

Spearheading this challenge is the International AIDS Society. Among the tasks: investigating where and how the virus can hide out in the body and studying the immune response of the select group of people who are naturally immune to HIV.

Developing drugs that keep HIV in check has so far proved more feasible than trying to eradicate it, said Dr. Steven Deeks, a member of the AIDS Research Institute at the University of California at San Francisco. But now that more than 20 antiretroviral therapies can prolong the lives of people with HIV for decades, he said, it's time to aim higher.

What changed? "It's come down to one man," said Paula Cannon, a molecular biologist at USC's Keck School of Medicine.

That man is Timothy Brown, known to the medical world as the Berlin Patient.

Brown was an HIV-positive American living in Germany when he developed leukemia. After failing to respond to first-line cancer treatments, he chose to have a bone marrow transplant in 2007. As his doctors sought a suitable donor, they looked for one with a rare genetic mutation that disables a receptor known as CCR5, which HIV needs to gain entry into immune cells. Brown had two transplants that not only put his leukemia into remission but also replaced his HIV-susceptible immune system with one that could ward off the disease.

Brown no longer takes antiretroviral drugs and no longer tests positive for HIV. Essentially, he is cured.

Researchers in California recently found traces of HIV in his tissues, but Brown says any remnants of the virus still in his body are dead and can't replicate.

He addressed the media in the United States for the first time Tuesday, appearing frail but energetic. He announced the formation of a new AIDS foundation in his name.

"There's nothing like success to galvanize the research," Cannon said. "People are daring to hope again that with a lot of hard work and ingenuity, scientists can deliver."

Bone marrow transplants aren't suitable for widespread use: The procedure Brown received ends in death 20 percent of the time, and finding an appropriate donor would be a long shot in most cases. So scientists are working on alternatives.

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There are two general approaches. One, an elimination cure, would rid the body of all HIV-infected cells. The other, a functional cure, would engineer a patient's own immune system to resist HIV, even if the virus remains present in the body.

For an elimination cure to work, researchers must learn to identify the dormant HIV that hides in immune cells and tissues, evading assault from drugs. Much of the International AIDS Society's plan focuses on this problem.

Efforts to flush the virus from its hiding places are showing signs of progress. For example, Dr. David Margolis, director of the Program in Translational Clinical Research at the University of North Carolina at Chapel Hill, and his colleagues have found that giving patients a drug called a histone deacetylase inhibitor can prompt HIV to wake up and start producing proteins. Drugs and the immune system can then recognize those proteins and mount an attack.

But it's far from clear how long this activation would last, or how to empty all of the hiding places. An effective elimination cure would also have to root out every last speck of HIV, including those in hard-to-reach areas like the brain and spleen.

One approach to a functional cure involves using gene therapy to modify a patient's DNA so that it produces immune cells with a disabled CCR5 gene. In theory, the result would be the same as with the Berlin Patient, said Dr. Jay Levy, who co-discovered the AIDS virus in 1983 and directs the Laboratory for Tumor and AIDS Virus Research at UCSF.

"It's going to be like going to the moon again, but it's so important that we do this," said Cannon, who is working on a gene-therapy project that could be ready for clinical trials in two years.

U.S. DEVOTES FUNDS: The United States is adding an extra $150 million to the global AIDS fight, taking a first step toward reaching some stigmatized populations. Despite tough fiscal times, "I am here today to make it absolutely clear the U.S. is committed and will remain committed to achieving an AIDS-free generation," Secretary of State Hillary Rodham Clinton told the International AIDS Conference on Monday.

That's a big goal: Some 34.2 million people worldwide are living with HIV, the virus that causes AIDS, and 2.5 million were infected last year.