Posted on 09/19/2005 2:27:12 AM PDT by Dane
Published: Sep 18, 2005 Modified: Sep 18, 2005 10:20 AM Triangle on front lines of war on AIDS Researchers note drug milestone
Womble tested positive for HIV in 1992.
By SABINE VOLLMER, Staff Writer
As a young man, John Paul Womble watched AIDS take his father's life. He watched him go blind and lose feeling in his hands. He never saw the purple lesions his father hid under makeup, but he knew the pain they caused.
Womble was 23 when his father, no longer able to stand the pain, committed suicide.
A year later, when Womble himself tested positive for HIV, he had little hope.
But his doctor, John A. Bartlett at Duke University, a pioneer in AIDS/HIV treatment, told him: "Son, you're going to beat this. You're going to become an old man."
Today, Womble is 37. He lives in Raleigh with his partner and works for an AIDS counseling service.
"I'm alive," he says, "because of AZT."
Azidothymidine, better known as AZT, was discovered as an AIDS drug in 1984 by scientists at Burroughs Wellcome, a smaller version of what is now GlaxoSmithKline in Research Triangle Park. It was the first breakthrough against the human immunodeficiency virus that causes AIDS.
On Saturday, AZT lost its patent protection. That means a cheaper, generic version will become available.
Interest in a drug coming off patent is usually only as great as the drug itself. In this case, a generic AZT means hope for millions in developing countries, for thousands in this country.
It is a milestone in the history of AIDS that will not go unmarked. While AZT is no longer the only treatment for HIV/AIDS, it led the way to other treatments.
"It was the first drug that attacked the disease by attacking the virus," said Dr. Dani Bolognesi, chief scientific officer of Trimeris, which two years ago began selling a first-of-its-kind AIDS drug. AZT, he said, was the first strategic step to outwit HIV.
Today 39 million adults and children worldwide are infected with HIV. The disease is transmitted through unsafe sex, contaminated needles and transfusions of contaminated blood. Pregnant women infected with HIV can pass it on to their unborn children. Some still take Retrovir, the name under which AZT is marketed, as part of a drug cocktail. Many take more powerful drugs containing AZT. Others may take drugs that do not include AZT, but most of those drugs attack the virus in the same way as AZT.
Whatever the treatment, it can most likely be traced back to the Triangle. That's because AZT did more than offer hope to AIDS sufferers: It established the Triangle as a hub for infectious disease research. GlaxoSmithKline, Gilead and Trimeris, three powerhouses in AIDS drug research, have operations in the Triangle. Duke University and UNC-Chapel Hill run two of the largest federally funded clinics in the nation to test AIDS drugs.
The Triangle is where the National Institutes of Health recently decided to base a $300 million effort to find an AIDS vaccine; where scientists are working on the first "oral entry inhibitor," a pill that would prevent the virus from entering other cells; and where a researcher is suggesting a cure may be within reach.
The Triangle scientists, physicians, social workers and advocates working on advancing AIDS treatment are a Who's Who in HIV/AIDS drug research and development.
'People were dying'
In the early 1980s, they were all just a bunch of scientists and doctors working around the clock to figure out why gay men were getting sick and dying of lung infections and a rare cancer.
"I vividly remember the earliest cases and how perplexing it was," said Dr. Charles Hicks, who worked in San Francisco in 1979 and '80. He remembers the emergency rooms there were the first stop for scores of gay men suffering from Kaposi's sarcoma, an uncommon cancer, and Pneumocystis carinii pneumonia, a lung infection known as PCP.
Physicians advised their patients to "get plenty of rest, keep yourself as healthy as you can, watch your nutrition," said Hicks, now an HIV/AIDS expert at Duke. "It was the same your mom would tell you."
The U.S. death toll mounted quickly: 10 in 1979, 42 in 1980, 219 in 1981, 739 in 1982 and 1,974 in 1983.
In 1982, the Centers for Disease Control gave the disease a name: Acquired Immune Deficiency Syndrome, or AIDS. The next year scientists identified the human immunodeficiency virus, or HIV, as its cause.
At Burroughs Wellcome, a 30-year-old researcher named Marty St. Clair was part of a small group of scientists working 12-hour days, sometimes seven days a week, to find a drug that would stop the disease.
"It was very intense," St. Clair recalled. "People were dying."
When they got worn down, the scientists would go to Duke Hospital and visit pediatric patients infected with HIV.
The visits, St. Clair said, motivated them even more. By 1984, they had developed a test using mouse cells infected with HIV to help them find a treatment.
Scientific advances in the past two decades have automated drug discovery -- machines can now run, evaluate and repeat up to 50,000 tests in three months.
But at Burroughs that year, St. Clair ran the tests herself, painstakingly, by hand.
From June to November, she put mouse cells on lab plates and infected the cells with HIV. Two hours later, she would add a chemical. Then, petri dishes holding the plates would go into an incubator heated to body temperature.
After four days, she added a dye to stain the mouse cells purple, and the liquid cell food was drained. When a chemical didn't work, clumps of dead cells, called plaques, drained along with the liquid. Then, St. Clair counted the holes the plaques had left by holding up each petri dish and marking up to 100 holes with a black Sharpie pen.
She had tested about 300 chemicals before she got to AZT, which was previously considered -- then shelved -- as a cancer treatment.
"The first time I tested AZT, there were no plaques," St. Clair said. She remembered turning to her supervisor Phillip Furman and telling him, " 'Oh my God, look, Phil. I must have forgotten to put virus in those plates.' "
In 18 of the plates she had pulled out of the incubator, no mouse cell had died. Those 18 contained AZT in varying concentrations.
That was late Friday afternoon, Nov. 16, 1984.
Over the weekend, word spread within Burroughs Wellcome.
When she returned to work on Monday to repeat the test, her answering machine was full of messages. People were stopping her in the hallways to ask: "Is it true? Is AZT active?"
"People were very excited," St. Clair said.
Early treatment
The Food and Drug Administration approved AZT -- marketed as Retrovir -- for sale on March 19, 1987. It had taken the drug about one-fifth of the time usually needed to pass regulatory requirements. Retrovir was in short supply for six months until Burroughs Wellcome could make enough to supply pharmacies.
Patients set their alarms to take Retrovir every four hours, said Hicks, the Duke physician. They put up with side effects, including nausea, fatigue and anemia, even after it became clear that Retrovir could delay symptoms only a year to 18 months because the virus managed to adapt and develop resistance to the drug.
"They did that because they were dying," he said. "This was their only glimmer of hope."
It was a glimmer that few could afford. Retrovir was the most expensive drug on the market. Initially, a year's supply cost up to $10,000 (the equivalent of $17,000 in 2005 dollars).
Under threats of a lawsuit and Congressional hearings, Burroughs Wellcome at the end of 1987 agreed to cut the cost of Retrovir by about 20 percent.
That wasn't enough for AIDS activists, especially the New York-based AIDS Coalition to Unleash Power, better known as ACT UP.
In April 1989, four ACT UP members briefly barricaded themselves into an office at Burroughs Wellcome's RTP headquarters. They were arrested, but charges were later dropped.
In the fall of 1989, Burroughs Wellcome cut the cost of Retrovir another 20 percent and lowered recommended dosages. That lowered the price for a year's supply to about $2,200.
But the company had more problems. In 1991, lawsuits by consumer advocates and generic drug makers questioned its rights to exclusively make and sell AZT.
Burroughs Wellcome had collaborated with the National Institutes of Health to prove AZT was effective against HIV. But the patent, filed Sept. 17, 1985, credits only Burroughs Wellcome scientists with the invention: St. Clair; her supervisor, Furman; Dr. Sandra Lehrman, who organized the clinical trials to test AZT in humans; Janet Rideout, the team's organic chemist; and Dr. David Barry, who headed the team.
The legal fight lasted five years. When the U.S. Supreme Court in 1996 let stand a ruling that affirmed Burroughs Wellcome's patent, the company had gone through two mergers, the FDA had approved five more AIDS drugs for sale, and a new class of powerful drugs, called protease inhibitors, were about to eliminate the "fatal" from HIV infection.
First father, then son
John Paul Womble tested positive for HIV in March 1992.
He had taken the test before, regularly, every six months, testing negative every time. But he knew this time was different.
On Christmas he had come down with debilitating, flulike symptoms.
The month before, on his 23rd birthday, he had engaged in risky, unprotected sex. Yes, he admits, he knew better. Better than most.
At the time, Womble was working part-time at the American Social Health Association, a Durham nonprofit that provides education about sexually transmitted diseases.
And there was his father, John Sidney Womble. A former Baptist preacher, the senior Womble had divorced, gone back to school to become an architect and left Raleigh in the late 1970s to live life as a well-to-do gay man in San Diego.
A photograph shows him a sandy-haired, fair-skinned man with Robert Redford good looks. The photograph was taken about four years after he tested positive in 1986. The first HIV test had become available in 1985.
His father took high doses of Retrovir as soon as the drug came on the market, John Paul Womble said. "I'm sure it halted the progression of the disease. But the damage was already done."
Knowing that Retrovir had been unable to save his father, John Paul Womble started making pacts with God on his way to be tested. He was, he remembers, sitting in his car, waiting at the stoplight in front of Peace College.
"I was pleading, 'God, will you please let this test be negative,' " he said. "When I received the results, I never thought I would see 30, let alone knock on 40."
But he began taking Retrovir -- two pills, three times a day with meals.
As a member of the second generation of AIDS sufferers, he was luckier than his father.
A year into his Retrovir treatment, Womble qualified for a clinical trial Duke was running to test 3TC, a drug that Glaxo Wellcome, another GSK predecessor, brought to market in 1995 as Epivir.
Swiss drugmaker Hoffman LaRoche came out with the first protease inhibitor the same year. Drugmakers Abbott and Merck followed in 1996. Glaxo Wellcome's version received regulatory approval in 1999.
Refining treatment
Protease inhibitors started the era of HIV/AIDS drug cocktails. At first, Womble said, the cocktails were fistfuls of pills that had to be taken according to a strict regimen.
Then, drugmakers managed to make combination drugs. The FDA approved Glaxo Wellcome's Combivir in 1997 and Trizivir in 2000. Both contain AZT.
In 2003, Trimeris introduced Fuzeon, the first "entry inhibitor," a drug that prevents the virus from entering another cell. Fuzeon is injected twice a day, but for longtime survivors it presents another hope to prolong life. GSK scientists are working on a pill that does the same.
The various drugs have done more than keep Womble alive. They have kept him healthy. He hasn't developed AIDS. And except for an AIDS-related cancer that has been in remission for almost four years, he has developed none of the telltale infections associated with AIDS.
The amount of virus in his body is nearly undetectably low. And his T cells -- infection-fighting cells found in blood and in the lymph system -- have increased. His count is close to 600 -- half the norm for a healthy male, but more than four times as high as when Womble first tested HIV positive.
He no longer takes a drug with AZT because he has developed a resistance to the chemical. But he can take five others that have been introduced since the mid-1990s.
All the various AIDS drugs have reduced the death rate by 70 percent, according to the Kaiser Family Foundation, a national health policy research group.
Today, more than 1 million men, women and children nationwide live with HIV infection.
After 20 years of searching for HIV's weaknesses, scientists now know: how the virus gets into a T cell; how the virus fools the T cell into accepting it; how it inserts itself into the cell's genetic material; how it then uses the cell to multiply by destroying the body's immune defenses; and how the virus can hide for years, almost undetectable but never idle, just waiting to step up its destructive work.
If HIV has an Achilles' heel, it has eluded researchers so far. Nobody has figured out yet how to rid a T cell of the virus.
But they are still trying.
St. Clair, now a senior virology researcher at GlaxoSmithKline, is still looking for new, better AIDS drugs.
"We're not done yet," she says
Is it just me or is the media hiding the well known facts that these treatments(AZT, etc.etc) also have debilitating side effects and it's best not to get HIV in the first place.
I just cannot work up any sympathy for "victims" of a 90%voluntarily acquired disease.
It is strange. One would THINK that he would have tried to avoid the same disease his father had. Was the father gay/bisexual also?
From the article, the father was a former Baptist preacher who moved to San Diego in the 70's to revel in the homosexual lifestyle.
Thanks! I missed the sentence and found it just now in re-reading. Like father, like son, eh?
I wonder if he's now taking Tenovir:
'It's OK, I'm on the AIDS Pill'
http://wired-vig.wired.com/news/print/0,1294,62436,00.html
[snip]
...What if tenofovir is 60 percent effective, but people who take it have 40 percent more unprotected sex?
Then there's the matter of other sexually transmitted diseases. If gay men refuse to wear condoms because they're "on the pill," an ongoing syphilis epidemic could conceivably get even worse.
As part of an HIV-prevention effort, health officials will provide intensive safer-sex education to all study participants in the United States and abroad. "It's going to be the best counseling we can give," said Dr. Grant Colfax, director of HIV-prevention studies in San Francisco, adding that all subjects in the city will have to pass a quiz to make sure they understand what they're getting into.
Not everyone is eager to take part in the study. "If I was taking the pill, I'd feel that I could probably take risks," said Chris Owen, associate program director of the Stop AIDS Project in San Francisco. "I'd rather not have that in the back of my mind."
You are spot on Dane. 90% of all US AIDs deaths during the AZT era (when treatment consisted of massive 1000 mg doses of AZT) died of liver failure. Massive liver damage is not caused by a virus, but by prolonged coercive treament with lethal toxins like AZT.
The "breakthrough" in AIDs treatment came when the results of the Concorde study were published - when it became blindingly obvious that AIDS is caused by the treatment for AIDS. It's been an iatrogenic disaster from start to finish.
There is no damn virus.
If there was it would be exogenous - it would be able to exist outside of the cell, even outside of the body. And it would have been isolated by now. But instead of admitting that they can't prove the HIV hypothesis, AIDS scientists have lowered the requirement of proof for viral isolation to where novel RNA in mitogenic culture is a new virus. No wonder it "mutates" all the time. (sigh)
"I'm alive," he says, "because of AZT."
Not really...you're alive only because God has let you live this long in order that you come to know the truth
Everybody dies...the question is...where will you, and those God made you responsible for, spend eternity?
Yet one more reason to recoil in disgust at the absurd ravings of the Left is their criticism of "Corporations" as "greedy" and "evil" and their contempt for capitalism and free enterprise. The Leftist morons are too dumb to understand--and the sociopaths who lead the Left are too cynical and self-serving to care--that capitalism is the generator of the economy that makes possible all the things they like--even their ability to be "Activists".
I wonder if Oprah--whom I deeply admire and respect--wise and thoughtful as she is, thinks about this when she ventures into the lunatic thought processes of the Left and if she is aware that capitalism is what made her great successes possible. I mean no disrespect to Oprah, but I do find disturbing her lack of disdain for Leftists and their agendas.
What about those who acquired it involuntarily?
And let us not forget who has been blamed for the AIDS epidemic. None other than a Republican President-Ronald Reagan. The liberals have not changed a bit. Now they are blaming Republicans for natural disasters as well.
That other 10%.
Later pingout - whoever gets to it first.
Homosexual Agenda Ping.
Faux history. Never mentions many of the basic facts - like what percentage of AIDS cases are either directly or indirectly because of what they term "men having sex with men". Never mentions the fact that AIDS is 100% preventable. Never mentions that a small but significant number of homosexual men go out of their way to GET AIDS. Or that a significant number know they test positive and go have anonymous sex anyway.
Never mentions that the amount of money spent on AIDS research, per person infected, far outweighs research money spent on diseases that aren't directly spread by pernicious sexual practices, such as heart disease and cancer.
Freepmail me AND DirtyHarryY2K if you want on/off this pinglist.
Not one word that people don't HAVE to be "gay", either.
http://www.freerepublic.com/focus/f-news/1420619/posts
Root Causes, Homosexual Consequences
Well, of course, you are right. Stay away from risky sexual behavbior, its as simple as that.
In other words, keep your pants up and don't bend over.
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