By Jim Schutze
By Rachel Watts
By Lauren Drewes Daniels
By Anna Merlan
By Lee Escobedo
By Eric Nicholson
Wayne Swearengin learned he had the HIV virus in 1989. Like everyone else diagnosed with the disease, he began searching for a drug regimen that would slow down the virus' march.
"I tried the AZT, but couldn't tolerate it," the 32-year-old Dallasite says. Since it was introduced in 1987, AZT has been considered the first line of defense against the progression of the disease. Swearengin tried D4T, which, like AZT, blocks the AIDS virus from entering cells, but is stronger. That drug caused numbness in his legs and feet. He learned last year his disease had developed into full-blown AIDS.
Five months ago, Swearengin's doctor offered him the chance to try the newest anti-AIDS drug under testing: a protease (pronounced PRO-tee-ace) inhibitor called saquinavir.
Saquinavir, produced by the Hoffman-La Roche pharmaceutical company, was designed to weaken and break down protease, a powerful enzyme in the AIDS virus. Protease, among other things, releases a protein that spreads the virus and also makes it infectious. As its name suggests, the new class of drugs inhibits the protease from releasing the protein.
Swearengin's doctor placed him in a Federal Drug Administration lottery, which randomly selected thousands of human guinea pigs on whom to test the drug. In the research, the drugs would be used in combination with other known anti-AIDS drugs like AZT.
When his name was selected to be the subject of a somewhat dicey experiment, Swearengin jumped at the chance. So far, things look good. "I went on it and didn't have any problems," he says.
The counts of his infection-fighting white cells, which had dropped to a dangerous 140, leaped back up to 360. He recovered a lot of lost energy and gained 45 pounds. And researchers found that the virus' activity inside him slowed down significantly.
"It did help," he says of saquinavir. "It does give you the feeling that you will be around a lot longer."
In January, saquinavir became the first drug of its kind to hit the market. Since then, under an FDA accelerated drug-approval program, the drug company Merck introduced indinavir and Abbott introduced ritonavir. At least two "third generation" protease inhibitors are under testing now.
The early successes of these pioneering drugs has the AIDS community abuzz. Protease inhibitors place pharmaceutical companies years ahead of the government in AIDS research and has given some AIDS patients a new lease on life. The emergence of the new drugs also comes at a time when researchers and practitioners are looking at new ways to monitor and fight the deadly disease, which has claimed more than 5,000 lives in Dallas alone since the late 1980s. For the first time in a long time, AIDS activists have a little something to celebrate, at least for now.
The drug has spawned dozens of almost miraculous success stories. Dr. Perry Pate, an infectious-disease specialist, says one of his patients was completely bedridden with pneumonia and micro-bacterium disease. After a few weeks of taking saquinavir, the virus activity decreased from a count of 500,000 to 10,000. (The higher the level of virus activity, the more likely the disease will progress.)
"He gained about 12 to 15 pounds and returned to full work and is doing well," Pate says. "It is uncommon to see people who are disabled for six months or more return to full work."
Dr. Steven Pounders, who treats AIDS patients, recalls that one of his patients in the late stages of the disease had developed a serious infection. "We started him on saquinavir and in three weeks his T-cell counts had jumped 400 points and he was leading physical therapists around the hallways and throwing dinner parties."
On ritonavir, Pounders says, patients covered from head to toe with Karposi's sarcoma sores watched the spots completely disappear in a matter of weeks.
"There have been dramatic improvements with these drugs like we have never seen before," Pounders says. "They are certainly more potent and have less side effects than with any of the previous ones. The problem is they become resistant fairly quickly. The low doses don't work very well, and the higher doses foster more resistant virus."
"I've been in this a long time," says Jack Emerson, research nurse at the Nelson-Tebedo Community Clinic in Dallas' Cedar Springs district. "It used to be that people were expected to live two or three years. Now we have people expecting to live more than 10 years after diagnosis, and a lot of it has to do with these drugs. Although they are not cures," Pate says, "they seem to prolong people's lives and that is the point to them."
Researchers hailed protease inhibitors at the Third Conference on Retroviruses and Opportunistic Infections in Washington, D.C., this January. In one test, protease inhibitors, when combined with other anti-AIDS drugs such has AZT, eliminated 99 percent of the AIDS virus detectable in the blood stream in most of the patients tested.
In Dallas, AIDS doctors, researchers, and activists are seeing a kind of "protease-inhibitor mania," says Pounders.
"There is a lot of enthusiasm for it," he says. "People often call and say, 'Tell me about those protease inhibitors.' It has been very exciting to treat HIV these past few months, more than it has ever been."
But everyone acknowledges the excitement may be short-lived. Although most recent tests are positive, the drugs also have researchers cautious, because they are so new. Many researchers fear the virus is simply lurking somewhere in the body, mutating, and waiting for an opportunity to reemerge in even more lethal forms. The drugs also have problems with absorption, some side effects, and bad reactions to other drugs important to the health of AIDS patients.
And not everyone who has added a protease inhibitor to his medication regimen got better.
Robert, a 38-year-old Dallas resident diagnosed with the AIDS virus 13 years ago, also tried saquinavir a year ago. But he experienced severe side effects with the drug, including complete numbness in his mouth and some paralysis in his legs. Although Robert has long had a low T-cell count (below 10), he never showed symptoms of the disease. He decided to discontinue use of the drug. "I was not willing to make that change, to sacrifice my good health," he says.
Skip Barnes, diagnosed with HIV in 1988, began taking ritonavir earlier this month. He decided to add the new drug to his regimen after seeing "all the hype on the protease inhibitors, about how they were possibly a breakthrough. I bought into the hype."
His experiment did not go well. "Before I started taking them," he says, "I was doing great. I was working part time. And then I started taking the ritonavir, and it started with the nausea and the numbness in my mouth, and then my skin felt like it was on fire."
After four days, he discontinued the use of ritonavir. "I decided I'd rather not be this sick."
Barnes has since begun taking smaller doses and says some of the side effects have slightly abated. "I am going to try and give it another shot. I'm hopeful that something will come out soon that doesn't have the side effects. I keep taking it because the virus doesn't seem to like it."
Because the drugs have been tested for a relatively short period of time (less than two years), they are still a mystery in many ways. "We don't have enough data to know all the answers," says Pate. "We don't know who are the best people to give this medicine to, or how long the benefits will last.
"But," he adds, "they are very potent agents and they give us tremendous strategies that will decrease (virus activity)."
The emergence of protease inhibitors also raises troubling questions about who is leading the fight against AIDS, Dallas experts say. "The goal is--if you can't find a cure--to make AIDS a chronic disease," says Emerson. "The question now is, do the drug companies want to find a cure or do they want to keep it at bay? It stands to reason that economically they would make more money to make this a chronic disease rather than to find a cure. They really need an uninterested party--the federal government--to step inside and find a vaccine."
Pharmaceutical companies are scrambling to build manufacturing plants for the drugs, which can exceed costs of $6,000 a year per patient.
The drugs are so expensive the Texas Department of Health announced this month it would not provide funding for making protease inhibitors available to the poor.
"It's unfortunate," Pate says, "because AIDS is a disease of the poor."
Testing is intensifying across the country and Dallas AIDS researchers and doctors closely monitor the results. This summer, the Nelson-Tebedo clinic will begin testing "third generation" protease inhibitors, says research nurse Jack Emerson. "The newer inhibitors coming out are significantly stronger than the ones on the market today."
And when they come out, Lloyd Duncan will begin taking them. Duncan, 31, has a T-cell count of 0, but the indinavir (widely considered the best of the lot) he has been taking has kept his virus activity down to such a minimum that the disease has not been able to progress as quickly as would be expected. "My doctor and I have an agreement that as the more aggressive drugs come out, I will switch to them," he says.
Duncan remembers the first time he learned of the protease inhibitors, in AIDS Update, a newsletter put out by the Foundation of Human Understanding in Dallas.
"I remember thinking it would be great if it was true," Duncan recalls. "There have been all kinds of drugs that have come out promising all types of stuff and half of them don't even work.
"I do know, though, that for me, the protease inhibitors have definitely stood up to everything that they promised.