Engine for medical advances
AIDS research driving developments in therapies for other diseases
By Carol Clark
CNN
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Protease inhibitors, developed for the treatment of AIDS, are being tested to fight other diseases such as hepatitis C.
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(CNN) -- Since it appeared on the scene 20 years ago, the virus that causes AIDS has invaded nearly every branch of medical science along with the bloodstreams of millions of people.
"AIDS has had a remarkable impact on medicine in ways that never could have been anticipated," said Mark Feinberg, a professor at Emory University School of Medicine and an AIDS researcher since 1984.
Scientists searching for solutions to the devastating effects of AIDS are making discoveries that could advance therapies for many other deadly diseases, he said.
"It's not just that we came up with new drugs. It's much more profound than that. We've been pushed to learn and be creative because of the AIDS epidemic. It's led to changes in the way we think about treating infectious diseases, autoimmune diseases and malignancies in general."
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Early in the epidemic, researchers pinpointed a virus -- HIV -- as the cause of AIDS. The intimate relationship that viruses form with a host cell made them impossible to eradicate through traditional drug therapies.
But the AIDS epidemic pushed researchers to develop new approaches to the virus problem. They eventually came up with two new classes of drugs -- reverse transcriptase inhibitors and protease inhibitors -- that were a landmark in the fight against viral diseases.
The drug lamivudine, a reverse transcriptase inhibitor developed to treat HIV, has proven to be the most effective therapy for chronic hepatitis B infection, Feinberg said. Millions of people around the world infected with hepatitis B, the leading cause of liver cancer, stand to benefit from the drug.
The second class of HIV drugs, protease inhibitors, are now under trial as a treatment for hepatitis C, another devastating disease.
"Until HIV came along, drug companies totally ignored these drugs as ways to attack viruses," said Jeffrey Laurence, director of laboratory AIDS research at Cornell University and a senior scientist at the American Foundation for AIDS Research (AmFAR). "The side effects were considered unworkable. But given the devastation of HIV, they tried them. These drugs are now very concrete examples of things that would never have been thought of if it hadn't been for AIDS."
HIV mutates rapidly and can quickly develop resistance to drugs. That led researchers to develop combination therapies, powerful drug "cocktails," to treat HIV patients. They also found ways to measure the level of virus in patients' systems -- a procedure called "viral load assay" -- to pinpoint when resistance to a particular drug starts. Like the new drugs, the new procedures hold promise for the treatment of viral infections in general.
'AIDS affects every part of the body'
The famed turn-of-the-century diagnostician William Osler once said that to know syphilis in all of its manifestations is to know "all things clinical."
The same statement now applies to AIDS, Laurence said. "AIDS affects every part of the body," he said. "To know it is to know medicine."
AIDS attacks the immune system, opening the door to opportunistic infections similar to the ones that threaten patients with advanced breast cancer who undergo bone marrow transplants in a last-ditch effort to fight the disease.
"A large portion of these women die from the infections after they receive the bone-marrow transplant," Laurence said. "The drugs that are being developed to help them fight off these infections are coming out of AIDS research."
Ultimately, advances in rebuilding the immune system in HIV patients will help people afflicted with many other illnesses tied to the immune system, including cancer, Alzheimer's disease and multiple sclerosis, according to AmFAR.
"With HIV you have one enemy that you can focus on," Laurence said. "Using AIDS as a simple model and getting it to work, you'll be closer to being able to put together more complex models, such as the ones that are needed for cancer."
Complications taking toll
As therapies were developed to treat the opportunistic infections associated with AIDS, patients began dying of other illnesses. One out of 10 adults with AIDS and one out of nine children are dying of heart disease, said Laurence, and an even higher percentage succumb to cancer.
Other complications of AIDS patients are bone loss leading to osteoporosis and diabetes.
These manifestations in AIDS patients are providing researchers with important clues to new therapies for these conditions. Many AIDS patients have willingly submitted to studies that are unlikely to help them personally but could benefit medical science in general, Laurence said.
"I've been overwhelmingly impressed with the willingness of people who have gone through so many tests to get stuck one more time because they realize that even if it maybe doesn't help them, it could help another person," he said.
Patient advocacy
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Activists have been a driving force in the battle against AIDS.
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People infected with HIV have long been a driving force in the fight against AIDS, starting a revolution in the way that science and government treat disease, said Jon Cohen, author of "Shots in the Dark: The Wayward Search for an AIDS Vaccine."
"HIV first struck the United States in gay men who were already politically organized," he said. "You had discrimination throwing fuel on the fire. On top of that you had a disease attacking primarily young people who have the energy to get out on the streets and shake their fists. People infected with HIV live many years in good health, and they can go out on the street and agitate. When you have lung cancer, you don't have the strength to do that."
The U.S. Food and Drug Administration "revamped itself significantly in reaction to AIDS, streamlining the approval process for all drugs," Cohen said.
"Now you see patient advocacy groups pushing for better treatments for breast cancer, Parkinson's and other diseases," Feinberg added. "That all started with the AIDS activist community pushing the issue in very public, very vocal and sometimes very dramatic ways. Those individuals, many of whom did not survive to see effective drug therapies, deserve a lot of the credit for their development."
Huge challenges ahead
The fight against AIDS is far from over. Scientists recently documented the first case of an HIV strain resistant to all current drugs, according to AmFAR. The organization estimates that as many as 10 percent of all new infections in the United States involve a strain of HIV that is resistant to at least one of the few anti-viral drugs now available.
"At this moment, statistically, the average number of years gained for patients with advanced AIDS, even with all these new drugs, is 1.8," Laurence said. "Just when you thought you were out of the woods and this has been converted into a chronic disease, you realize that the years gained on these powerful therapies are relatively minor."
The HIV virus mutates each time it divides, and it divides every eight to 12 hours, Laurence said.
The United Nations estimates that 36.1 million people worldwide are infected with HIV, and thousands of new infections are transmitted each day.
When the AIDS epidemic first appeared, some top researchers predicted that an HIV vaccine would be developed within a few years. Nearly two decades later, a vaccine has yet to materialize.
"In the area of vaccine research, there's not been a major interest in the part of large pharmaceutical companies," Feinberg said. "Merck and a couple of smaller companies have trials, but given the need, the level of activity is rather small."
But Feinberg said he believes that the search for an AIDS vaccine eventually will be successful and yield benefits beyond combating AIDS. "We're already gaining new strategies for making more effective vaccines," he said. "We've got a better understanding of how vaccines work. Just like HIV drug research has changed how we pursue the development and use of drugs, I think HIV vaccine research is going to change the way we think of developing vaccines."
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