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In search of a cure, scientists look for where HIV hides

February 7, 2014 at 6:31 PM EDT
While scientists and doctors have hopes of helping the 34 million people infected with HIV live disease-free, some basic questions remain about the virus, like where it hides in the human body. Special correspondent Spencer Michels reports on the latest steps in the search for an AIDS cure and renewed support from the government.
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JUDY WOODRUFF: The battle against AIDS, which began in the early 1980s and has succeeded in finding treatments to control the disease, is increasingly turning to a different phase: the hunt for a real and complete cure.

Special correspondent Spencer Michels has our story.

SPENCER MICHELS: Fifty-seven-year-old Matt Sharp, who has had AIDS for 25 years, takes a mix of antiretroviral drugs each day to reduce his HIV levels and keep him alive.

Sharp, a former ballet dancer, says the medication has shortened his life, and makes him more susceptible to other ailments, like heart disease earlier than normal.

MATT SHARP: I’m faced with issues around growing older earlier because of having HIV for so long. I have been taking pills for over 25 years. I’m ready for a point where I can do something that my body can control the virus on its own.

SPENCER MICHELS: Sharp has volunteered for studies now under way that, if successful, could eliminate the need for a lifetime of powerful pills.

Scientists and medical doctors are working both in the lab and in clinical settings to find out more about HIV, especially where it lurks, and to find out how patients will respond to experimental treatments. The idea, of course, is to completely eradicate the HIV.

DR. MIKE MCCUNE, University of California, San Francisco: What we really want to do is make it so that the people around the world, all 34 million of them infected with HIV, can lead a disease-free life without having to take antiretrovirals for the rest of their lives.

SPENCER MICHELS: Mike McCune, professor of medicine at the University of California, San Francisco, has been in the forefront of AIDS research since the beginning, and he’s watched the progress of research, including some spectacular successes.

A few patients around the world have apparently been cured of AIDS and attracted international attention. An infected American who got a bone marrow transplant in Berlin is disease-free, as is a baby in Mississippi who was treated at birth. These cases have raised hopes that the virus can be eliminated entirely, curing the disease.

But two Boston patients whom doctors thought were cured had the virus return. None of those cases has led to a universal treatment. And so, in December, the White House and the National Institutes of Health endorsed a full-fledged research program towards finding a cure.

PRESIDENT BARACK OBAMA: We’re going to redirect $100 million into this project to develop a new generation of therapies.

SPENCER MICHELS: For McCune and his team, the key task today is finding the virus. He knows that antiretroviral drugs keep the patient alive and kill much of the HIV. But, invariably, some virus remains hidden and causes the patients’ health to decline.

 

DR. MIKE MCCUNE: What we don’t know is where in the human body it lives.

SPENCER MICHELS: Researchers in McCune’s labs and elsewhere study tissue taken from clinical subjects to look at places they think the virus may be hiding.

DR. MIKE MCCUNE: It’s often organs, organs like the intestinal track, the spleen, the liver, the brain and elsewhere. We want to know which cells it lives in, whether it be dormant or latent or actively replicating or spreading.

Some drugs, for instance, go to the spleen very easily, but don’t go to the brain. Maybe we need two or three drugs to go to two or three different patterns.

SPENCER MICHELS: McCune’s basic research is aimed at finding how the hidden AIDS virus behaves, and how to make it show itself so it can be killed or induced to commit suicide.

At the nearby University of California-affiliated Gladstone Institute, Dr. Warner Greene, who is also doing basic research, says finding the few cells infected with virus is not easy. Their hiding places are called reservoirs.

DR. WARNER GREENE, Gladstone Institute: The reservoir is only established on one cell in a million. So it’s a needle in a haystack. Or it’s like, where in the world is Waldo? Finding and identifying that latently infected cell is virtually impossible, because the virus is not expressing any of its proteins. It’s slumbering.

SPENCER MICHELS: This time-lapse video shows T-cells, key to the immune system, being attacked and killed by HIV. In Greene’s lab, researchers first have to find the cell harboring the virus using small molecules to make it show itself

DR. WARNER GREENE: And either the cell automatically dies, or now the immune system can attack, can be directed to those cells to destroy the reservoir.

SPENCER MICHELS: So you call this?

DR. WARNER GREENE: Shock and kill. But there are problems. We know that when we deliver the shock, not all the cells that we want to get shocked get shocked. And we also know that once — even those that are successfully shocked, they don’t necessarily get killed.

SPENCER MICHELS: The key to success is to kill them all, but they’re not there yet.

DR. WARNER GREENE: We take the drugs away and, sure enough, within a matter of a few weeks, the virus bounces back to levels established before the antiretroviral drugs were administered.

SPENCER MICHELS: A private company, Calimmune, is using a different strategy. The idea is to harvest the patient’s own cells, modify them with stem cells, and return them to the patient, so they can defeat the virus.

Louis Breton, the CEO, says the firm, which gets support from California’s publicly-funded Stem Cell Agency, is already in clinical trials, taking blood from patients, and modifying the genes.

LOUIS BRETON, CEO, Calimmune: If you can defend the body first, you have the opportunity to potentially then eradicate the virus. We are looking at working on a one-time outpatient procedure that would treat a patient’s own cells, modify them to protect them, and give them back to the patient.

DR. WARNER GREENE: This is really at the technological edge and is very exciting work. Gene therapy could potentially be scalable for the developing world, if it involved a single injection.

SPENCER MICHELS: For patients like 49-year-old John Caldera and his physician, Steve Deeks, the promise of a simple cure is alluring, but remote.

JOHN CALDERA: I have been on at least 10 research studies where it was experimental drugs, and I rolled the dice. I would love to see a future where there is no HIV, and I think we’re very close.

DR. STEVE DEEKS, University of California, San Francisco: OK. You’re good.

SPENCER MICHELS: But Deeks, a clinical professor at U.C. San Francisco, isn’t so sure a cure is imminent.

DR. STEVE DEEKS: With some of these more aggressive approaches, gene therapy and stem cell transplants and so forth, the risk is much greater, but the reward is also potentially much greater, because it’s theoretically possible to cure people with a single intervention. It’s possible. I don’t think anyone thinks its likely. But it’s certainly worth trying.

SPENCER MICHELS: Deeks says the few patients who have been cured of AIDS so far lead to one conclusion.

DR. STEVE DEEKS: There’s going to be many roads, many paths to take. And it’s going to be a combination of shock and kill, an increase in the capacity of the immune system to kill the virus, and increase in the capacity of the immune system to control the virus, and probably ultimately getting people on therapy super, super early to prevent the virus from spreading early on.

SPENCER MICHELS: Whatever approaches are used, most researchers, and the NIH, agree that the work is in its very early stages, and barring a surprise development, it could be years before a real cure for AIDS, and an affordable one, is found.